subject:(RGS)

1. Windhol, Cindy E. Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models.

Degree: PhD, Molecular Pharmacology, Physiology, and Biotechnology, 2012, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:297558/

► Cardiac myocytes (CM) and fibroblasts (CF) are the two major cell types in the heart. Overall, cardiac remodeling occurs in response to stress on the… (more)

▼ Cardiac myocytes (CM) and fibroblasts (CF) are the two major cell types in the heart. Overall, cardiac remodeling occurs in response to stress on the heart which alters the structural components of the myocardium. Both cell types play an essential role in cardiac remodeling. Enhanced Gq/11-mediated signaling is well known to activate CM and CF and to induce structural and electrical remodeling, making this pathway a therapeutic target. Gq/11-mediated signal transfer can be mitigated by Regulators of G protein Signaling (RGS). Of the major RGS proteins expressed in the heart, only RGS2 is considered to be selective in negatively regulating Gq/11. We have created a CM-specific transgenic overexpression of RGS2 to delineate whether RGS2 can inhibit Gq/11-mediated signaling and hypertrophy development. Despite ample evidence suggesting that RGS2 is a functionally important negative regulator of Gq/11 signaling and hypertrophy, CM-specific transgenic RGS2 overexpression did not lead to attenuation of Gq/11-mediated hypertrophy in our model. In the atria from transgenic mice, effective inhibition of Gq/11 signaling was observed, indicating functionality of transgenic RGS2 protein at the level expressed even after aortic constriction (TAC). In contrast, in RGS2-expressing ventricles, Gq/11 signaling was not inhibited after TAC which likely underlies the lack of anti-hypertrophic effect observed in RGS2-expressing mice. Cardiac fibroblasts increasingly attract attention as direct therapeutic targets. We identified RGS2 as a novel, functionally important, negative regulator of angiotenisin II-induced signaling and function in CF that is highly regulated by angiotensin II. Overall, RGS2 may emerge as a therapeutic target in cardiac fibroblast as it mitigates Gq/11 protein-mediated fibroblast activation. Gq-mediated signaling is well known to activate CM and CF but the extent to which Gq signaling is enhanced in each cell type and the extent to which CM affect CF (and vice versa) are unclear. We have therefore developed a micropatterned 2D co-culture model with spatially defined configurations to lay the groundwork for studies on the crossregulation of the two major cardiac types both under normal and diseased conditions. Advisors/Committee Members: Mende, Ulrike (Director), Harrington, Elizabeth (Reader), Oancea, Elena (Reader), Padbury, James (Reader), Liao, Ronglih (Reader).

Subjects/Keywords: RGS proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Windhol, C. E. (2012). Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:297558/

Chicago Manual of Style (16^th Edition):

Windhol, Cindy E. “Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models.” 2012. Doctoral Dissertation, Brown University. Accessed January 15, 2021. https://repository.library.brown.edu/studio/item/bdr:297558/.

MLA Handbook (7^th Edition):

Windhol, Cindy E. “Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models.” 2012. Web. 15 Jan 2021.

Vancouver:

Windhol CE. Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models. [Internet] [Doctoral dissertation]. Brown University; 2012. [cited 2021 Jan 15]. Available from: https://repository.library.brown.edu/studio/item/bdr:297558/.

Council of Science Editors:

Windhol CE. Understanding the Role of Regulator of G-Protein Signaling 2 (RGS2) in Cardiac Systems and In Vitro Models. [Doctoral Dissertation]. Brown University; 2012. Available from: https://repository.library.brown.edu/studio/item/bdr:297558/

University of Toronto

2. Danaf, Jamil. G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression.

Degree: 2020, University of Toronto

URL: http://hdl.handle.net/1807/103521

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Opioids are pain treatment mainstays, but present with potentially lethal respiratory depression. To develop safer opioid therapies, mechanisms underlying opioid-induced respiratory depression must be better… (more)

Subjects/Keywords: Opioid; PreBotzinger Complex; Respiratory Depression; RGS; 0306

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Danaf, J. (2020). G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/103521

Chicago Manual of Style (16^th Edition):

Danaf, Jamil. “G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression.” 2020. Masters Thesis, University of Toronto. Accessed January 15, 2021. http://hdl.handle.net/1807/103521.

MLA Handbook (7^th Edition):

Danaf, Jamil. “G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression.” 2020. Web. 15 Jan 2021.

Vancouver:

Danaf J. G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression. [Internet] [Masters thesis]. University of Toronto; 2020. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/1807/103521.

Council of Science Editors:

Danaf J. G-protein Signaling Regulating Opioid-induced Respiratory Rate Depression. [Masters Thesis]. University of Toronto; 2020. Available from: http://hdl.handle.net/1807/103521

3. Gaspari, Sevasti. A role of RGS proteins in opiate actions.

Degree: 2018, University of Crete (UOC); Πανεπιστήμιο Κρήτης

URL: http://hdl.handle.net/10442/hedi/42432

► Opioids are among the most effective medications used for the alleviation of severe pain conditions, but their long-term use is hindered by the development of… (more)

▼ Opioids are among the most effective medications used for the alleviation of severe pain conditions, but their long-term use is hindered by the development of analgesic tolerance, dependence and addiction. Understanding the molecular mechanisms underlying their analgesic effects and the adaptations leading to the development of the undesirable side-effects would be a significant contribution towards improving chronic pain treatment. Falling within this rational, the present thesis focused on examining the role of regulator of G-protein signaling (RGS) proteins in opiate actions. RGS proteins possess a wide and diverse family of proteins known to mediate G-protein coupled receptor (GPCR) signaling duration and direction, through their interaction with heterotrimeric Gα subunits. Here, we study the role of two RGS family members that modulate Mu opioid receptor (MOPR) mediated signaling, RGS9-2 and RGSz1. Particularly, the thesis is consisting of three specific aims:Aim I examined if and how RGS9-2 modulates responses to oxycodone both in pain-free conditions and under chronic pain states. RGS9-2 is predominantly expressed in the striatum and it has been shown to exert a critical role on the MOPR signaling. It is a negative regulator of morphine analgesia and reward, while at the same time it promotes the development of morphine tolerance. In contrast, RGS9-2 appears as a positive modulator of other MOPR agonist, such as methadone and fentanyl. Here we investigate its role as a regulator of another MOPR agonist widely used and abused over the last years, oxycodone. Using transgenic mice lacking the Rgs9 gene (RGS9KO), we observed that RGS9-2 positively regulates the rewarding effects of oxycodone both in pain-free states and in a model of neuropathic pain. Furthermore, although RGS9-2 does not affect the acute analgesic efficacy of the drug, it opposes the development of oxycodone tolerance. Overall, these results provide new information on the signal transduction mechanisms underlying the analgesic and rewarding actions of oxycodone.Aim II is focused on the role of RGSz1 in opiate actions. RGSz1 is a small RGS protein primarily expressed in brain tissue, that exhibits high specificity for Gαz subunits and has been shown to act downstream of MOPR and serotonin receptor 1A (Htr1A). Using genetic mouse models for constitutive or conditional/brain region-targeted manipulations of RGSz1 expression, we demonstrated that the analgesic efficacy of several MOPR agonists is increased by preventing RGSz1 actions both in male and female mice. In addition, prevention of RGSz1 action delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using next-generation RNA sequencing combined with further biochemical12assays examining protein expression and localization, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. We show that chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates…

Subjects/Keywords: RGS πρωτεΐνες; Πόνος; Οποιοειδή; Μορφίνη; Οξυκωδόνη; Διαγονιδιακά ποντίκια; RGS proteins; Pain; Opioids; Morphine; Oxycodone; Transgenic mice

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gaspari, S. (2018). A role of RGS proteins in opiate actions. (Thesis). University of Crete (UOC); Πανεπιστήμιο Κρήτης. Retrieved from http://hdl.handle.net/10442/hedi/42432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gaspari, Sevasti. “A role of RGS proteins in opiate actions.” 2018. Thesis, University of Crete (UOC); Πανεπιστήμιο Κρήτης. Accessed January 15, 2021. http://hdl.handle.net/10442/hedi/42432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gaspari, Sevasti. “A role of RGS proteins in opiate actions.” 2018. Web. 15 Jan 2021.

Vancouver:

Gaspari S. A role of RGS proteins in opiate actions. [Internet] [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2018. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10442/hedi/42432.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gaspari S. A role of RGS proteins in opiate actions. [Thesis]. University of Crete (UOC); Πανεπιστήμιο Κρήτης; 2018. Available from: http://hdl.handle.net/10442/hedi/42432

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. Wesström, Josefin. Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet.

Degree: Care and Social Welfare, 2017, Mälardalen University

URL: http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37222

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Bakgrund: Telefonsjuksköterskors arbetsuppgifter är att råda, stötta och göra bedömningar i en komplex situation. Studier har gjorts på telefonsjuksköterskors erfarenhet i telefonrådgivning men få… (more)

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Bakgrund: Telefonsjuksköterskors arbetsuppgifter är att råda, stötta och göra bedömningar i en komplex situation. Studier har gjorts på telefonsjuksköterskors erfarenhet i telefonrådgivning men få har inkluderat observation. Syfte: Denna studie syftar till att beskriva hur telefonsjuksköterskor använder webbaserat beslutsstöd i telefonrådgivning på vårdcentral och deras erfarenheter av detta. Metod: Studien är kvalitativ med beskrivande design. Observationer och halvstrukturerade intervjuer utfördes på vårdcentral. Sex distriktssköterskor som hade arbetat minst ett år i telefonrådgivning deltog. Analys: Data från observationerna och intervjuerna bearbetades med kvalitativ innehållsanalys. Resultat: Telefonsjuksköterskorna använde dataprogrammet Rådgivningsstödet Webb (RGS Webb) som en stödjande funktion vilket skapade trygghet. För stora textmassor med långa sökvägar försvårade arbetet. Faktorer som organisatorisk tidspress, avsaknad av hjälpmedel för kommunikation med patienter som talar annat språk och lång erfarenhet minskade användandet av RGS Webb. Diskussion: Telefonsjuksköterskorna upplevde stöd i att RGS Webb gav mycket och korrekt information som kunde ges till vårdtagare. Detta ledde till säkrare bedömningar som ökade patientsäkerheten. RGS Webb upplevdes svårarbetat med mycket textmassor. Utbildning behövs inom informationsteknik eftersom sjuksköterskorna idag förväntas vara stora användare av IT. Slutsats: RGS Webb stödjer, påminner, skapar trygghet och ger ny kunskap. Svårigheter som fanns utgjorde hinder i användandet och RGS Webb användes i mindre utsträckning eller inte alls.

Background: The telephone nurse's duties are to advise, support and make assessments in a complex situation. Studies have been conducted on the telephone nurse's experience in telephone counseling, but few have included observation. Aim: This study aims at describing how telephone nurses use computer decision support system in telephone counseling at the health center and their experiences with this. Method: The study is qualitative with descriptive design. Observations and semi-structured interviews were conducted at the health center. Six district nurses who had worked for at least one year in telephone consulting participated. Analysis: The data from the observations and interviews were processed using qualitative content analysis. Result: The telephone nurse used the computer decision support system (RGS Webb) as a supportive feature, which created security. Too large text pads with long paths made work difficult. Factors such as organizational time pressure, lack of tools for communication with patients who speak other languages and long experience reduced the use of RGS Webb. Discussion: The telephone nurse found support in the fact that RGS Webb provided very accurate information that could be given to caregivers. This leads to safer assessments that increase patient safety. RGS Webb was experienced hard-working with a lot of text…

Subjects/Keywords: District Nurse; Primary Care; RGS Web; Telephone counseling; Triage; Distriktssköterska; Primärvård; RGS Webb; Telefonrådgivning; Triage; Nursing; Omvårdnad

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wesström, J. (2017). Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet. (Thesis). Mälardalen University. Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37222

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wesström, Josefin. “Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet.” 2017. Thesis, Mälardalen University. Accessed January 15, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37222.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wesström, Josefin. “Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet.” 2017. Web. 15 Jan 2021.

Vancouver:

Wesström J. Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet. [Internet] [Thesis]. Mälardalen University; 2017. [cited 2021 Jan 15]. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37222.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wesström J. Hur webbaserat beslutstöd används i telefonrådgivning på vårdcentral : Telefonsjuksköterskors erfarenheter av beslutstödet. [Thesis]. Mälardalen University; 2017. Available from: http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-37222

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Λεοντιάδης, Λεωνίδας. Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες.

Degree: 2012, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/37676

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Opioid receptors belong to the superfamily of G protein coupled receptors (GPCRs) and regulate analgesia and tolerance-dependence to narcotic drugs. A new family of proteins,… (more)

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Opioid receptors belong to the superfamily of G protein coupled receptors (GPCRs) and regulate analgesia and tolerance-dependence to narcotic drugs. A new family of proteins, RGS proteins (Regulators of G protein Signalling), are involved in the signalling of GPCRs by accelerating the rate of GTP hydrolysis from Gα subunits, thus terminating signal transduction. The aim of the research was to study the interactions of μ- and δ-opioid receptors (μ-OR, δ-OR) with RGS4 protein and the role of RGS4 in receptor signalling. In vitro pulldown experiments using GST-/MBP-fusion peptides demonstrated that RGS4 binds to the third intracellular loop and the conserved region of the carboxyl tails of opioid receptors (μ-CT, δ-CT). RGS4 functions as a scaffold protein and promotes the binding of Gα subunit to the μ-CT, forming a RGS4–Gα–μ-CT ternary complex. Co-immunoprecipitation experiments showed that RGS4 promotes interaction of μ-OR, δ-OR with specific Gα subunit subtypes, depending on receptor activation. Functional experiments demonstrated that RGS4 a) increases intracellular cAMP accumulation by reducing opioid receptor adenyl cyclase inhibition, b) inhibits ERK phosphorylation, c) colocalizes with activated receptors. The N terminal of RGS4 is responsible for the protein’s functional activity. The results of this study indicate that RGS4 protein is a key element for the regulation and specificity of opioid receptor signalling.

Οι οπιοειδείς υποδοχείς ανήκουν στους υποδοχείς που συζεύγνυνται με G πρωτεΐνες (GPCRs) και ρυθμίζουν την αναλγησία και την ανοχή-εξάρτηση σε ναρκωτικές ουσίες. Στη σηματοδότηση των GPCRs εμπλέκεται μια νέα οικογένεια πρωτεϊνών, οι RGS πρωτεΐνες (Regulators of G protein Signaling), που επιταχύνουν το ρυθμό υδρόλυσης του GΤΡ από τις Gα υπομονάδες, τερματίζοντας έτσι τη μετάδοση του ερεθίσματος. Σκοπός της διατριβής ήταν να μελετηθούν οι αλληλεπιδράσεις των μ- και δ-οπιοειδών υποδοχέων (μ-OR, δ-OR) με την RGS4 πρωτεΐνη και ο ρόλος της RGS4 στη σηματοδότησή τους. Πειράματα in vitro πρόσδεσης με τη χρήση GST-/MBP-χιμαιρικών πεπτιδίων απέδειξαν ότι η RGS4 προσδένεται στην τρίτη ενδοκυτταρική θηλιά και στο συντηρημένο τμήμα των καρβοξυτελικών άκρων των οπιοειδών υποδοχέων (μ-CT, δ-CT). Η RGS4 λειτουργεί επίσης ως ικρίωμα και προάγει την πρόσδεση της Gα υπομονάδας στο μ-CT, σχηματίζοντας ένα ετεροτριμερές σύμπλοκο RGS4–Gα–μ-CT. Πειράματα συν-ανοσοκατακρήμνισης έδειξαν ότι η RGS4 προάγει την αλληλεπίδραση των μ-OR, δ-OR με συγκεκριμένους υποτύπους Gα υπομονάδων, ανάλογα με την κατάσταση ενεργοποίησης των υποδοχέων. Λειτουργικά πειράματα έδειξαν ότι η RGS4 α) μειώνει την αναστολή της αδενυλικής κυκλάσης, αυξάνοντας τα ποσοστά του διαθέσιμου ενδοκυτταρικού cAMP, β) αναστέλλει τη φωσφορυλίωση των ERK κινασών, γ) συνεντοπίζεται με τους ενεργοποιημένους υποδοχείς. Για αυτές τις λειτουργικές επιδράσεις ευθύνεται το αμινοτελικό άκρο της RGS4. Τα αποτελέσματα της διατριβής δεικνύουν ότι η RGS4 πρωτεΐνη είναι ένα μόριο-κλειδί για την ρύθμιση και εξειδίκευση της σηματοδότησης των οπιοειδών υποδοχέων.

Subjects/Keywords: Οπιοειδείς υποδοχείς; RGS πρωτεϊνες; Αλληλεπίδραση πρωτεϊνών; Πρωτεϊνικά σύμπλοκα; Εξειδίκευση σηματοδότησης; Opioid receptors; RGS proteins; Protein interactions; Protein complexes; Signalling specificity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Λεοντιάδης, . �. (2012). Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/37676

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Λεοντιάδης, Λεωνίδας. “Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες.” 2012. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed January 15, 2021. http://hdl.handle.net/10442/hedi/37676.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Λεοντιάδης, Λεωνίδας. “Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες.” 2012. Web. 15 Jan 2021.

Vancouver:

Λεοντιάδης �. Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2012. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10442/hedi/37676.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Λεοντιάδης �. Λειτουργικές αλληλεπιδράσεις πρωτεϊνών με υποδοχείς που συζεύγνυνται με G πρωτεΐνες. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2012. Available from: http://hdl.handle.net/10442/hedi/37676

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. Bastin, Guillaume. Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function.

Degree: Docteur es, Ingénierie des fonctions biologiques, 2013, Université Lille I – Sciences et Technologies

URL: http://www.theses.fr/2013LIL10003

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Les protéines RGS (Regulator of G-protein Signaling) sont des inhibiteurs des voies de signalisation des protéines G. RGS4 atténue l’activité de protéines G dans plusieurs… (more)

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Les protéines RGS (Regulator of G-protein Signaling) sont des inhibiteurs des voies de signalisation des protéines G. RGS4 atténue l’activité de protéines G dans plusieurs tissus tel que la diminution de son activité peut accroître la sévérité de la bradycardie, cardiomyopathies liées au diabète, l’invasion de cellule cancéreuse du sein, résistance à l’insuline et intolérance au glucose. RGS4 a été localisé à la membrane plasmique ainsi que dans des compartiments intracellulaires, cependant, son mode de trafique intracellulaire reste méconnu. En utilisant des outils de microscopie confocale sur cellules vivantes et méthode de détection d’activité des voies de signalisation conditionnée par les protéines G, nous avons caractérisé l’importance de deux sites de palmitoylation, ces deux sites : Cys2 et Cys12 montrent des intérêts complémentaires dans le trafic de RGS4 vers la membrane cellulaire. Dans un axe linéaire, nous avons identifié DHHC3 et 7, deux enzymes de palmitoylation participant au trafique intracellulaire de RGS4 et donc à la maximalisation de son activité inhibitrice des voies de signalisation contrôlées par Galphaq. Enfin des marqueurs de membranes endosomales, les protéines rab ont permis de caractériser les voies de trafic intracellulaire empruntée par RGS4, par exemple RGS4 est internalisé de la membrane plasmique par Rab5 et recyclé à la membrane cellulaire par Rab11. L’activation ou inhibition de Rab5 et 11 ont permis d’observer des changements d’activité de RGS4. Ces travaux confèrent une base de données pour des études ultérieures visant à développer des stratégies thérapeutiques à accroître les fonctionnalités de RGS4.

RGS proteins (Regulator of G-protein Signaling) are potent inhibitors of heterotrimeric G-protein signaling. RGS4 attenuates G-protein activity in several tissues such that loss of its function may lead to bradycardia, diabetic cardiomyopathy, breast cancer cell invasion, insulin resistance and glucose intolerance. RGS4 has been localized to both plasma membrane and intracellular pools, however, the nature of its intracellular trafficking remains to be elucidated. G-protein inhibition requires the presence of RGS4 at the plasma membrane. In this work, we characterized the complementary roles of two putative palmitoylation sites on RGS4 to target intracellular compartments and plasma membrane. We identified palmitoylation on Cys2 and 12 respectively important for RGS4 endosomal targeting and plasma membrane localization, when mutations were introduced to the palmitoylation sites, RGS4 capability of inhibiting Gq-mediated signaling was impaired. As a continuum we identified two palmitoylating enzymes, DHHC3 and 7 as modulator of RGS4 localization and function. Knock downs of DHHC3 and 7 impaired RGS4 endosomal and plasma membrane targeting and capability of inhibiting M1-muscarinic receptor signaling. Finally we used live cell confocal microscopy to define RGS4 intracellular trafficking routes. Specifically Rab5 mediated RGS4 trafficking from the plasma membrane to intracellular…

Advisors/Committee Members: Rolando, Christian (thesis director), Heximer, Scott (thesis director).

Subjects/Keywords: Protéines RGS; Protéines DHHC; Protéines Rab; Palmitoylation; Trafic intracellulaire; 547.7

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bastin, G. (2013). Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function. (Doctoral Dissertation). Université Lille I – Sciences et Technologies. Retrieved from http://www.theses.fr/2013LIL10003

Chicago Manual of Style (16^th Edition):

Bastin, Guillaume. “Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function.” 2013. Doctoral Dissertation, Université Lille I – Sciences et Technologies. Accessed January 15, 2021. http://www.theses.fr/2013LIL10003.

MLA Handbook (7^th Edition):

Bastin, Guillaume. “Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function.” 2013. Web. 15 Jan 2021.

Vancouver:

Bastin G. Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function. [Internet] [Doctoral dissertation]. Université Lille I – Sciences et Technologies; 2013. [cited 2021 Jan 15]. Available from: http://www.theses.fr/2013LIL10003.

Council of Science Editors:

Bastin G. Les résidus cystéines en positions 2 et 12 de RGS4 influencent son trafic intracellulaire et ses fonctions : RGS4 cysteine residues at positions 2 and 12 influence its intracellular trafficking and function. [Doctoral Dissertation]. Université Lille I – Sciences et Technologies; 2013. Available from: http://www.theses.fr/2013LIL10003

University of Texas Southwestern Medical Center

7. Ocal, Ozhan. Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes.

Degree: 2012, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/1034

► Diabetes mellitus is a collection of metabolic diseases with chronic hyperglycemia as their common syndrome. Type 1 diabetes results from pancreatic insulin producing beta cell… (more)

▼ Diabetes mellitus is a collection of metabolic diseases with chronic hyperglycemia as their common syndrome. Type 1 diabetes results from pancreatic insulin producing beta cell loss due to autoimmune attack and consequent insulin insufficiency, whereas type 2 diabetes occurs as a result of somatic cell insulin resistance under metabolic stress. Therapies include insulin supplementation for type 1 diabetics and diet control and augmented insulin release for type 2 diabetics. G-protein coupled receptors (GPCR) represent the largest non-antibiotic drug targets and several family members are expressed in beta cells. Regulators of G-protein Signaling (RGS) proteins are feedback regulators of GPCRs. Their expression can be induced by GPCR or cross-talk signals to inhibit GPCR pathway, thereby indicating when and where GPCR signaling occurs. Our studies utilizing Rgs16::GFP transgenic mouse previously showed that Rgs16 was expressed in embryonic pancreatic progenitor cells, endocrine cells, and postnatal vessel and ductal associated cells (VDAC). Euglycemic adults lacked pancreatic Rgs16::GFP expression. We investigated diabetic mice to determine if Rgs16::GFP would reactivate during beta cell expansion in adulthood. The type 1 diabetic models of beta cell death were streptozotocin (STZ) treatment and PANIC-ATTAC mice. Type 2 diabetic models consisted of ob/ob mice and diet induced obesity. In each case, Rgs16::GFP expression initiated in islets and VDAC after at least 6 days of chronic hyperglycemia. STZ induced Rgs16::GFP expression was reduced after lowering blood glucose levels with systematic insulin administrations. Furthermore, hyperglycemia dependent Rgs16::GFP expression required metabolic transcription factor Carbohydrate Response Element Binding Protein (ChREBP), as pancreatic Rgs16::GFP was absent in STZ-treated ChREBP KO mice. We found that Rgs16::GFP is also expressed in Pancreatic Ductal Adenocarcinoma (PDAC) tumors and primary tissue culture cells. RNA-Seq analysis revealed that cultured PDAC cells express many genes in common with embryonic progenitors of ductal and endocrine cells and identified expression of 63 GPCRs. In summary, our results suggest that Rgs16::GFP is stimulated by GPCR signals relayed from a "hyperglycemia sensor". We propose that Rgs16 is a faithful pancreatic biomarker of diabetes and Rgs16::GFP PDAC culture and diabetic reporter mice are beneficial resources to identify ligands that stimulate beta cell expansion without promoting cancer. Advisors/Committee Members: Wilkie, Thomas.

Subjects/Keywords: Diabetes Mellitus, Type 1; RGS Proteins; Receptors, G-Protein-Coupled

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ocal, O. (2012). Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1034

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ocal, Ozhan. “Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes.” 2012. Thesis, University of Texas Southwestern Medical Center. Accessed January 15, 2021. http://hdl.handle.net/2152.5/1034.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ocal, Ozhan. “Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes.” 2012. Web. 15 Jan 2021.

Vancouver:

Ocal O. Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2012. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2152.5/1034.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ocal O. Rgs16 is a Pancreatic Reporter of Chronic Hyperglycemia in Diabetes. [Thesis]. University of Texas Southwestern Medical Center; 2012. Available from: http://hdl.handle.net/2152.5/1034

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

8. Schneider, Patricia Neiva Coelho. Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions.

Degree: PhD, Genetics, 2010, University of Iowa

URL: https://ir.uiowa.edu/etd/598

► Upon sperm entry, the vertebrate egg undergoes a series of cell divisions that create a number of smaller cells without increasing the embryonic mass.… (more)

▼ Upon sperm entry, the vertebrate egg undergoes a series of cell divisions that create a number of smaller cells without increasing the embryonic mass. This induces an elevation of intracellular calcium transient that is conserved across species. In zebrafish, fertilization occurs through an opening in the chorion, the micropyle and in Xenopus it can occur anywhere in the animal hemisphere. Wnt signaling activation is required during dorsal-ventral axis specification and it needs to be suppressed during the regionalization of the brain. Axin is a negative regulator of Wnt signaling and contains an RGS (Regulator of G Protein Signaling) domain. RGS domains are typical of RGS proteins, which are involved in a distinct signaling pathway, G-protein signaling. RGS proteins exert a negative effect of G-protein signaling by accelerating the GTPase activity (GAP) of the Gα subunit, thus turning off the signaling. Axin contains an RGS domain, however, it is not clear whether Axin is directly involved in G-protein signaling. We will also present a work performed using another negative regulator of the Wnt signaling network called naked cuticle (Nkd). Nkd has been shown to modulate β-catenin dependent and independent Wnt signaling. In chapter 2, we will show that the Axin-RGS like function is dispensable during the formation of the dorsal-ventral axis. We manipulated this protein by creating a point mutation in a critical aminoacid within the Axin-RGS domain, known to be detrimental for the GAP function of RGS proteins, Axin1Q162A. Maternal depletion of Axin1 in Xenopus oocytes causes hyperactivation of Wnt signaling and results in dorsalization. Axin1Q162A is able to suppress the dorsalization of maternally depleted embryo and restore normal dorsa-ventral axis formation. In chapter 3, we will describe the role of Axin during the patterning of the vertebrate brain. We show that the point mutant is not able to restore normal brain development in zebrafish embryos after Axin knockdown. We hypothesize that Axin-RGS like function is necessary during the patterning of the vertebrate brain that occurs after zygotic transcription has been initiated. Moreover, we show that Axin-RGS like activity may be dispensable during this stage of development. Finally, we demonstrate that Axin1Q162A localization differs from the wildtype Axin1 and Axin1 but not Axin1Q162A is localized to the plasma membrane upon Gα overexpression in zebrafish embryos. Embryonic organ laterality is preceded by molecular and physiological asymmetries. In chapter 4 we describe the role of another Wnt antagonis, Nkd cuticle, during left-right patterning. Prior to organogenesis, a group of cells called Dorsal Forerunner Cells, (DFCs), migrate ahead of the dorsal blastoderm during gastrulation to form the Kupffer's vesicle (KV). This vesicle will trigger a signaling cascade that will culminate with left-right determination. We show data that support the requirement of Nkd in organ laterality and convergence and extension movements using zebrafish and… Advisors/Committee Members: Houston, Douglas W. (Douglas William) (supervisor).

Subjects/Keywords: Axin; RGS; Wnt; Genetics

…an RGS (Regulator of G Protein Signaling) domain. RGS domains are typical of RGS… …proteins, which are involved in a distinct signaling pathway, G-protein signaling. RGS proteins… …x29; of the Gα subunit, thus turning off the signaling. Axin contains an RGS domain, however… …independent Wnt signaling. In chapter 2, we will show that the Axin-RGS like function is dispensable… …point mutation in a critical aminoacid within the Axin-RGS domain, known to be detrimental for…

12 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schneider, P. N. C. (2010). Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/598

Chicago Manual of Style (16^th Edition):

Schneider, Patricia Neiva Coelho. “Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions.” 2010. Doctoral Dissertation, University of Iowa. Accessed January 15, 2021. https://ir.uiowa.edu/etd/598.

MLA Handbook (7^th Edition):

Schneider, Patricia Neiva Coelho. “Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions.” 2010. Web. 15 Jan 2021.

Vancouver:

Schneider PNC. Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions. [Internet] [Doctoral dissertation]. University of Iowa; 2010. [cited 2021 Jan 15]. Available from: https://ir.uiowa.edu/etd/598.

Council of Science Editors:

Schneider PNC. Role for the Axin-RGS domain during embryonic development: maternal vs. zygotic functions. [Doctoral Dissertation]. University of Iowa; 2010. Available from: https://ir.uiowa.edu/etd/598

9. DIANA CORNELIO. Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae).

Degree: 2013, UNIVERSIDADE ESTADUAL DE PONTA GROSSA

URL: http://www.bicen-tede.uepg.br/tde_busca/arquivo.php?codArquivo=1046

► Astyanax scabripinnis é uma espécie encontrada na Região Neotropical, essa espécie forma demes populacionais isolados em cabeceiras de riachos. Ela é taxonomicamente mal resolvida, mas… (more)

▼ Astyanax scabripinnis é uma espécie encontrada na Região Neotropical, essa espécie forma demes populacionais isolados em cabeceiras de riachos. Ela é taxonomicamente mal resolvida, mas se apresenta como interessante modelo para o estudo da presença de cromossomos B. A ocorrência desses cromossomos em A. scabripinnis pode estar associada a diversos fatores ambientais e populacionais, embora seja pouco esclarecido sobre a manutenção parasítica ou possíveis efeitos heteróticos desses cromossomos. A biologia reprodutiva relacionada à presença de cromossomo B em A. scabripinnis nunca foi abordada. Assim, foi objeto deste trabalho investigar se aspectos do processo reprodutivo, fundamental para o valor adaptativo, podem estar relacionados à presença de cromossomos B em A. scabripinnis. As coletas foram realizadas trimestralmente entre os anos de 2012 e 2013 na região de Campos do Jordão, São Paulo, Brasil (2240`49,5S, 4523`31,9 W), no Córrego da Fazenda Lavrinha, bacia do rio Paraíba do Sul. As gônadas foram classificadas macro e microscopicamente segundo estádios de desenvolvimento. Estabeleceu-se sazonalmente a proporção sexual da população nas diferentes amostragens. Foi calculada a relação gonadossomática (RGS) e a relação hepatossomática (RHS) separadamente para fêmeas com e sem cromossomo B. A presença de cromossomos B foi confirmada por meio da citogenética clássica e molecular com o emprego de sonda específica do cromossomo B construída por microdissecção cromossômica e amplificação por Degenerated Oligonucleotids Primers (DOP-PCR) e posterior hibridação fluorescente in situ (FISH). Análises de morfometria geométrica foram realizadas separadamente para fêmeas e machos com e sem a presença de cromossomos B. Os resultados indicam que a proporção sexual variou sazonalmente havendo um aumento do número dos machos em relação às fêmeas. Foram encontrados indivíduos hermafroditas na frequência de 7,7%. O período reprodutivo é caracterizado por um pico de reprodução atípico no período do inverno, além do período padrão observado a partir da primavera no mês de setembro. A presença de cromossomos B foi relacionada a possíveis estratégias reprodutivas distintas na população estudada, especialmente em relação ao aporte energético e estádios de desenvolvimento gonadal. Há diferenças morfométrica tanto entre indivíduos fêmeas e machos como entre indivíduos com e sem cromossomo B. Advisors/Committee Members: Mara Cristina de Almeida, Roberto Ferreira Artoni, Orlando Moreira Filho, Thais Saad Sczepanski.

Subjects/Keywords: RGS; RHS; proporção sexual; FISH; citogenética; GSR; HSR; sex ratio; FISH; cytogenetics; BIOLOGIA MOLECULAR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

CORNELIO, D. (2013). Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae). (Thesis). UNIVERSIDADE ESTADUAL DE PONTA GROSSA. Retrieved from http://www.bicen-tede.uepg.br/tde_busca/arquivo.php?codArquivo=1046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

CORNELIO, DIANA. “Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae).” 2013. Thesis, UNIVERSIDADE ESTADUAL DE PONTA GROSSA. Accessed January 15, 2021. http://www.bicen-tede.uepg.br/tde_busca/arquivo.php?codArquivo=1046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

CORNELIO, DIANA. “Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae).” 2013. Web. 15 Jan 2021.

Vancouver:

CORNELIO D. Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae). [Internet] [Thesis]. UNIVERSIDADE ESTADUAL DE PONTA GROSSA; 2013. [cited 2021 Jan 15]. Available from: http://www.bicen-tede.uepg.br/tde_busca/arquivo.php?codArquivo=1046.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

CORNELIO D. Biologia reprodutiva e presença de cromossomo B em Astyanax scabripinnis (Teleostei: Characidae). [Thesis]. UNIVERSIDADE ESTADUAL DE PONTA GROSSA; 2013. Available from: http://www.bicen-tede.uepg.br/tde_busca/arquivo.php?codArquivo=1046

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas Southwestern Medical Center

10. Waugh, Jeffrey Lynn. A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins.

Degree: 2005, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/705

► The regulators of G-protein signaling (RGS) proteins negatively modulate heterotrimeric G protein signaling by acting as GTPase activating proteins for Galpha subunits. In the striatum… (more)

▼ The regulators of G-protein signaling (RGS) proteins negatively modulate heterotrimeric G protein signaling by acting as GTPase activating proteins for Galpha subunits. In the striatum and nucleus accumbens, brain regions critical for control of movement, motivation and reward, overlapping RGS expression profiles suggested that functional specificity could not be explained by anatomical localization alone. We set out to assess striatal specificity within two distinct RGS pools, the R7 RGS subfamily and RGS10. The highly striatal-specific splice form RGS9-2 is a negative modulator of dopamine D2 receptor signaling, and has been shown to inhibit drug stimulated (cocaine or direct dopamine receptor agonists) locomotor activity. RGS9-2 is a member of the R7 subfamily, comprised of RGS6, -7, -9, and -11, which share highly similar subdomain structure. We analyzed the specificity of R7 modulation of dopamine receptor signaling using a novel behavioral assay. R7 RGS proteins were virally-overexpressed in rat or mouse accumbens via a stereotaxic injection of an engineered HSV virus. Following this surgery, drug-stimulated locomotor responses were assayed. We found that in rats and RGS9 KO mice, overexpression of R7 RGS proteins produces distinct locomotor and drug sensitization phenotypes, each of which occurs only during the period of RGS overexpression. Moreover, studies using truncation and chimeric RGS mutants demonstrated that while all tested subdomains were necessary for activity, only the C-terminus of RGS9-2 was sufficient to convey activity to RGS7. Lastly, RGS overexpression leads to distinct acute changes in weight: loss (RGS9-2) or gain (RGS7, RGS11). To elucidate RGS10 function in the brain, we mapped RGS10 protein in rodent brain using light microscopic and electron microscopic immunohistochemical techniques. Light microscopic analyses showed that RGS10 immunoreactivity labels all subcompartments of neurons and microglia, including their nuclei. Electron microscopy confirmed the presence of dense RGS10 immunoreactivity in euchromatin and resolved dense staining on terminals at symmetric synapses onto pyramidal cell somata. Dual-labeling histochemistry showed that RGS10 is expressed in specific neuronal cell types and circuits. Taken together, these data support a role for RGS10 in diverse processes including modulation of pre- and postsynaptic G-protein signaling and a potential role in modulating gene expression. Advisors/Committee Members: Gold, Stephen J..

Subjects/Keywords: RGS Proteins; Synaptic Transmission; Gene Expression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Waugh, J. L. (2005). A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/705

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Waugh, Jeffrey Lynn. “A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins.” 2005. Thesis, University of Texas Southwestern Medical Center. Accessed January 15, 2021. http://hdl.handle.net/2152.5/705.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Waugh, Jeffrey Lynn. “A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins.” 2005. Web. 15 Jan 2021.

Vancouver:

Waugh JL. A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2005. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2152.5/705.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Waugh JL. A Structural/Behavioral Analysis of the Regulation of Dopamine Signaling by Striatal RGS Proteins. [Thesis]. University of Texas Southwestern Medical Center; 2005. Available from: http://hdl.handle.net/2152.5/705

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Iowa

11. Freisinger, Christina M. Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning.

Degree: PhD, Biology, 2010, University of Iowa

URL: https://ir.uiowa.edu/etd/667

► The process of vertebrate development requires communication among many cells of the embryo in order to define the body axis (front/back, head/tail or left/right).… (more)

▼ The process of vertebrate development requires communication among many cells of the embryo in order to define the body axis (front/back, head/tail or left/right). The Wnt signaling network plays a key role in a vast array of cellular processes including body axis patterning and cell polarity. One arm of the Wnt signaling network, the non-canonical Wnt pathway, mediates intracellular Ca²⁺ release via activation of heterotrimeric G proteins. Regulator of G protein Signaling (RGS) proteins can accelerate inactivation of G proteins by acting as G protein GAPs and are uniquely situated to control the amplitude of a Wnt signal. I hypothesize that individual RGS proteins are critical in modulating the frequency and amplitude of Wnt/Ca²⁺ signaling in different tissues and at different developmental stages and this modulation is essential for developmental patterning events. To this end, this thesis is focused on the effects G protein regulation has on intracellular Ca²⁺ release dynamics and developmental patterning events. I combine cellular, molecular and genetic analyses with high resolution Ca²⁺ imaging to provide new understanding of the role of RGS proteins on Wnt mediated Ca²⁺ release dynamics and developmental patterning events. In chapter 2, I describe endogenous Ca²⁺ dynamics from the very first cell divisions through early somitogenesis in zebrafish embryos. I find that each phase of zebrafish development has a distinct pattern of Ca²⁺ release, highlighting the complexity of Ca²⁺ ion and cellular physiology. In Chapter 3, I identify rgs3 as potential modulator of Ca²⁺ dynamics and Chapter 4 expands upon these observations by providing data supporting that Rgs3 function is necessary for appropriate frequency and amplitude of Ca²⁺ release during somitogenesis and that Rgs3 functions downstream of Wnt5 activity. My results provide new evidence that a member of the RGS protein family is essential for modulating the non-canonical Wnt network to assure normal tissue patterning during development. In Chapter 5, I report the identification and characterization of Rgs3b, a paralogue to Rgs3, in zebrafish. I describe results indicating that Rgs3b is poised to interact with Wnt11 indicating that individual RGS genes may have unique roles in modulating Wnt/Ca2+ signaling in different tissues or different stages. In conclusion, this thesis provides data supporting that individual RGS proteins are critical in modulating the frequency and amplitude of Wnt/Ca²⁺ signaling in different tissues and at different developmental stages and this is a substantial breakthrough in understanding how RGS proteins function to fine-tune known signaling pathways Advisors/Committee Members: Slusarski, Diane C. (supervisor).

Subjects/Keywords: G Protein; RGS; Wnt; Zebrafish; Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Freisinger, C. M. (2010). Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/667

Chicago Manual of Style (16^th Edition):

Freisinger, Christina M. “Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning.” 2010. Doctoral Dissertation, University of Iowa. Accessed January 15, 2021. https://ir.uiowa.edu/etd/667.

MLA Handbook (7^th Edition):

Freisinger, Christina M. “Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning.” 2010. Web. 15 Jan 2021.

Vancouver:

Freisinger CM. Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning. [Internet] [Doctoral dissertation]. University of Iowa; 2010. [cited 2021 Jan 15]. Available from: https://ir.uiowa.edu/etd/667.

Council of Science Editors:

Freisinger CM. Regulator of G protein signaling 3 modulates Wnt5b calcium dynamics and somite patterning. [Doctoral Dissertation]. University of Iowa; 2010. Available from: https://ir.uiowa.edu/etd/667

University of Manchester

12. Ko, Daniel. RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia.

Degree: PhD, 2012, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/rgs-proteins-in-experimental-parkinsonism-and-ldopainduced-dyskinesia(97c4a365-d9d5-48fb-8ccd-9c653b801427).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559314

► Parkinson’s disease (PD) is a progressive neurodegenerative disorder producing a clinical syndrome of bradykinesia, rigidity and resting tremor. These motor symptoms appear due to the… (more)

▼ Parkinson’s disease (PD) is a progressive neurodegenerative disorder producing a clinical syndrome of bradykinesia, rigidity and resting tremor. These motor symptoms appear due to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and loss of dopamine in the striatum, which subsequently leads to an imbalance of the basal ganglia motor circuit. The most effective pharmacological treatment for PD is L-3,4-dihydroxyphenylalanine (L-DOPA), the immediate metabolic precursor of dopamine, which effectively restores motor function. L-DOPA is catabolised into dopamine and replaces neurotransmitter loss in PD. However, long-term L-DOPA treatment leads to abnormal involuntary movements (AIMs), such as L-DOPA-induced dyskinesia (LID), which reduces the quality of life in PD patients. Currently, there are no reliable pharmacological treatments for these motor complications. Clinical and preclinical studies have shown that development and expression of LID is linked to unregulated dopamine release and plasticity-induced changes of striatal dopaminergic and non-dopaminergic signalling pathways. The activities of these pathways can be modulated by neurotransmitter receptors of a specific classification, the G-protein-coupled receptor (GPCR) family. In turn, GPCRs are regulated by certain endogenous proteins, the regulators of G-protein signalling (RGS) proteins. Numerous RGS protein subtypes are expressed in the striatum but their roles in PD and LID remain poorly understood. Given the modulatory function of RGS proteins in the striatum, these endogenous factors may have pathophysiological roles in the expression of motor symptoms in PD and LID. The studies presented in this thesis investigated the roles of RGS proteins in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and LID. Rats received unilateral 6-OHDA lesions of the right medial forebrain bundle to induce severe dopamine denervation. L-DOPA/benserazide (6/15 mg/kg) was then administered once daily for at least 21 days to induce stable abnormal involuntary movements (AIMs). In Chapter 2 of this thesis, increased levels of RGS2 and RGS4 mRNA were found in the rostral striatum of the unilateral 6-OHDA-lesioned rat model of LID. Moreover, elevated levels of RGS4 mRNA were specific to sensorimotor regions and positively correlated with AIMs severity. These molecular and behavioural data suggest that RGS4 proteins are involved in the expression of LID. In Chapters 3 and 4, behavioural studies conducted in the unilateral 6-OHDA-lesioned rat model of LID showed that acute inhibition of striatal RGS4 proteins reduced the expression of AIMs and improved overall motor function. Moreover, repeated de novo treatment with RGS4 protein inhibitors, in combination with L-DOPA, attenuated the development of AIMs and reduced the overexpression of preproenkephalin-B, a molecular marker of LID. These behavioural and molecular data suggest that blockade of RGS4 proteins can reduce the induction of LID. In Chapter 5, in vivo microdialysis…

Subjects/Keywords: 616.833; RGS proteins; Parkinson's disease; L-DOPA-induced dyskinesia; RGS4; 6-hydroxydopamine

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ko, D. (2012). RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/rgs-proteins-in-experimental-parkinsonism-and-ldopainduced-dyskinesia(97c4a365-d9d5-48fb-8ccd-9c653b801427).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559314

Chicago Manual of Style (16^th Edition):

Ko, Daniel. “RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia.” 2012. Doctoral Dissertation, University of Manchester. Accessed January 15, 2021. https://www.research.manchester.ac.uk/portal/en/theses/rgs-proteins-in-experimental-parkinsonism-and-ldopainduced-dyskinesia(97c4a365-d9d5-48fb-8ccd-9c653b801427).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559314.

MLA Handbook (7^th Edition):

Ko, Daniel. “RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia.” 2012. Web. 15 Jan 2021.

Vancouver:

Ko D. RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia. [Internet] [Doctoral dissertation]. University of Manchester; 2012. [cited 2021 Jan 15]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/rgs-proteins-in-experimental-parkinsonism-and-ldopainduced-dyskinesia(97c4a365-d9d5-48fb-8ccd-9c653b801427).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559314.

Council of Science Editors:

Ko D. RGS proteins in experimental Parkinsonism and L-DOPA-induced dyskinesia. [Doctoral Dissertation]. University of Manchester; 2012. Available from: https://www.research.manchester.ac.uk/portal/en/theses/rgs-proteins-in-experimental-parkinsonism-and-ldopainduced-dyskinesia(97c4a365-d9d5-48fb-8ccd-9c653b801427).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559314

University of Iowa

13. Bodle, Christopher Ralph. Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies.

Degree: PhD, Medicinal and Natural Products Chemistry, 2017, University of Iowa

URL: https://ir.uiowa.edu/etd/5420

► Regulator of G-protein Signaling (RGS) proteins temporally regulate the G protein signaling cascades initiated by GPCR activation. Reports have established dysregulation of RGS expression… (more)

▼ Regulator of G-protein Signaling (RGS) proteins temporally regulate the G protein signaling cascades initiated by GPCR activation. Reports have established dysregulation of RGS expression in a variety of disease states including several cancers. Additionally, use of genetic ablation techniques has implicated RGS proteins in a variety of other disease states through the native action of the RGS i.e. not a consequence of dysregulation of RGS expression. Therefore identification and optimization of small molecule lead compounds that alter RGS protein function has emerged as a promising therapeutic strategy. In this thesis, we use high throughput screening to interrogate small molecule libraries targeting two RGS proteins, RGS6 and RGS17. RGS6 has been reported as an essential mediator of doxorubicin induced cardiotoxicity, alcohol induced cardio and hepatotoxicity, anxiety, depression, and alcohol dependence. RGS17 has largely been implicated in a variety of cancer pathogenesis, with reported over expression in prostate, lung, breast, and hepatocellular carcinomas. Chapter 2 of this work focuses on the screening efforts targeting RGS6. Three separate screening campaigns interrogating over 20K compounds led to the identification of 3 small molecules that inhibit the RGS6: Gαo protein protein interaction with appreciable selectivity over control assays. The development of a cell based protein interaction assay is discussed, and the compounds were investigated using this system. All compounds tested did not appreciably alter signal over control, meaning that the cellular activity of these compounds remains ambiguous. Chapter 3 details the screening and follow up efforts targeting RGS17. The primary screening and/or follow up of four separate screening campaigns interrogating over 110K compounds is discussed. In total, 10 identified leads and a panel of analogs were subjected to significant follow up evaluation. All compounds were found to be cysteine dependent. The second generation RGS17 inhibitors (UI series) were determined to be both cytostatic and cytotoxic against lung and prostate cancer cell lines in culture, although whether this is due to RGS17 dependent mechanisms or due to general promiscuity of the compounds remains to be determined. Lead compounds from a library provided by the NCI were found to have cellular activity and were subjected to an investigation of structure activity relationships via commercially available compounds. The active form of three of these compounds was found to be a degradation product, which is likely due to decomposition of furan or methyl furan moieties that these compounds shared. One compound demonstrated robust SAR which allowed for the generation of schemes detailing putative inhibitory mechanisms. Finally, the role of RGS17 in the transition from epithelial to mesenchymal phenotypes is investigated. RGS17 was found to cause a sub population of PC3 cells to shift to mesenchymal phenotype, indicating that RGS17 may indeed play a role in this transition.… Advisors/Committee Members: Roman, David L. (supervisor).

Subjects/Keywords: Alcoholism; Cancer; Depression; G protein; High Throughput Screening; RGS; Pharmacy and Pharmaceutical Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bodle, C. R. (2017). Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/5420

Chicago Manual of Style (16^th Edition):

Bodle, Christopher Ralph. “Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies.” 2017. Doctoral Dissertation, University of Iowa. Accessed January 15, 2021. https://ir.uiowa.edu/etd/5420.

MLA Handbook (7^th Edition):

Bodle, Christopher Ralph. “Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies.” 2017. Web. 15 Jan 2021.

Vancouver:

Bodle CR. Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies. [Internet] [Doctoral dissertation]. University of Iowa; 2017. [cited 2021 Jan 15]. Available from: https://ir.uiowa.edu/etd/5420.

Council of Science Editors:

Bodle CR. Identification of small molecule inhibitors of regulator of G protein signaling proteins for pretherapeutic development for treatment of multiple pathologies. [Doctoral Dissertation]. University of Iowa; 2017. Available from: https://ir.uiowa.edu/etd/5420

University of Pennsylvania

14. Hannanta-Anan, Pimkhuan. Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling.

Degree: 2018, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/3126

► Calcium is a fundamental secondary messenger responsible for relaying information from the extracellular space to the cell interior. Extracellular cues are temporally encoded through calcium… (more)

▼ Calcium is a fundamental secondary messenger responsible for relaying information from the extracellular space to the cell interior. Extracellular cues are temporally encoded through calcium signals, which often arise in the form of oscillations. These oscillations are then decoded to inform cellular decisions and regulate cellular functions. Despite its crucial role in cell signaling, the encoding and decoding of calcium oscillations is poorly understood. The current biological tools and methods used to study calcium signaling lack the temporal precision and specificity necessary to precisely manipulate, perturb, and dissect calcium signaling circuits. To address this need, we developed a new set of optogenetic techniques to regulate calcium signaling circuits and study calcium encoding and decoding. First, we created optogenetic RGS2 (opto-RGS2) for studying calcium encoding. A light-induced hetero-dimerization system was engineered to recruit the RGS2 domain to the membrane where it interacted with its cognate G protein. Using our engineered opto-RGS2 cell line, we revealed that RGS2 reduced periodicity and stochasticity of G-protein coupled calcium oscillations and acted as a feedback regulator in this signaling circuit. Our opto-RGS2 addresses the need for better tools to perturb calcium signaling circuits and will enable future studies in calcium encoding. Next, we developed an optogenetic method to dissect mechanisms of calcium decoding. The amplitude, frequency, and duty cycle of calcium oscillations are the principal components driving calcium-coupled cellular functions. However, how these components individually contribute to the overall calcium decoding is unknown. Using a mathematical model, an optogenetically-engineered cell line, and custom hardware, we optically re-created patterns of calcium oscillations that independently varied a single waveform component. By monitoring calcium-coupled transcription, we revealed that the calcium-dependent transcription factor NFAT was more sensitive to the duty cycle of calcium oscillations as opposed to the oscillation frequency. Therefore, NFAT acted primarily as a signal integrator rather than a frequency decoder as previously hypothesized. With our new optogenetic approach, we isolated the role of individual signaling components and resolved a prevailing and controversial question in calcium decoding. In summary, we developed novel optogenetic approaches and applied them to answer key questions in calcium encoding and decoding.

Subjects/Keywords: CALCIUM SIGNALING; NFAT; OPTOGENETICS; REGULATORS OF G-PROTEIN SIGNALING (RGS); Molecular Biology; Systems Biology

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APA (6^th Edition):

Hannanta-Anan, P. (2018). Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/3126

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hannanta-Anan, Pimkhuan. “Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling.” 2018. Thesis, University of Pennsylvania. Accessed January 15, 2021. https://repository.upenn.edu/edissertations/3126.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hannanta-Anan, Pimkhuan. “Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling.” 2018. Web. 15 Jan 2021.

Vancouver:

Hannanta-Anan P. Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling. [Internet] [Thesis]. University of Pennsylvania; 2018. [cited 2021 Jan 15]. Available from: https://repository.upenn.edu/edissertations/3126.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hannanta-Anan P. Decoding Calcium Encoding Through Bi-Directional Optogenetic Control Over Gq-Protein Signaling. [Thesis]. University of Pennsylvania; 2018. Available from: https://repository.upenn.edu/edissertations/3126

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Michigan

15. Senese, Nicolas. Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors.

Degree: PhD, Pharmacology, 2017, University of Michigan

URL: http://hdl.handle.net/2027.42/140971

► Multiple classes of drugs, including antidepressants as well as opioid analgesics, exert their therapeutic effects at least in part by direct or indirect actions at… (more)

▼ Multiple classes of drugs, including antidepressants as well as opioid analgesics, exert their therapeutic effects at least in part by direct or indirect actions at G-protein-coupled receptors (GPCR’s). This class of receptor propagates a signal inside the cell by activating heterotrimeric G-proteins (comprised of Gα and Gβγ subunits). Following receptor activation GDP bound to the Gα subunit of the heterotrimer is exchanged for GTP, followed by separation of the Gα and Gβγ subunits. Both Gα and Gβγ then activate downstream signaling pathways inside the cell. The regulator of G-protein signaling (RGS) proteins are a class of intracellular regulatory proteins that serve as negative modulators of GPCR signaling. They exert their actions by binding to active Gα-GTP subunits and accelerating the hydrolysis of GTP to GDP with subsequent reformation of the Gα/βγ heterotrimer, thus terminating signaling. In this work, I describe the use of mice expressing Gα subunits of one of two types (either Gαi2 or Gαo) that do not bind to RGS proteins and so are RGS insensitive (RGSi) to gain a better understanding of how RGS proteins regulate both antidepressant-like and antinociceptive behaviors. Site-specific microinjections of a serotonin 1A receptor (5HT1AR) antagonist and agonist are used to show that mice expressing RGSi Gαi2 have a robust antidepressant-like phenotype dependent on hippocampal 5-HT1AR activity. Ex vivo recording from hippocampal tissue confirms that a 5-HT1AR agonist inhibits cellular activity more effectively in mice expressing RGSi Gαi2. Furthermore, I demonstrate that hippocampal administration of an RGS4/19 inhibitor (CCG203769) produces antidepressant-like effects. I show that mice expressing RGSi Gαo have a complex phenotype including increased and decreased sensitivity to noxious stimuli consistent with alterations in both nociceptin receptor (NOPR) and mu opioid receptor (MOPR) activity. The balance between the antinociceptive MOPR and pronociceptive NOPR systems is disturbed in the RGSi Gαo mice and in wild type mice during inflammatory pain. This work expands upon previous findings showing profound differences between mice with enhanced signaling downstream of different Gαi/o proteins due to the loss of RGS control, and provides novel information regarding the receptor systems and brain regions involved, with implications for both the treatment of depressive disorders and pain. This work is significant because it provides a greater understanding of the G-proteins involved in the perception of pain and depression, as well as the receptor systems and RGS proteins that control their activity. Advisors/Committee Members: Traynor, John R (committee member), Mosberg, Henry I (committee member), Beg, Asim (committee member), Gnegy, Margaret E (committee member), Jutkiewicz, Emily M (committee member).

Subjects/Keywords: Regulator of G-protein Signaling; Antidepressant; Analgesic; Pharmacology; RGS insensitive G-protein; G-protein coupled Receptor; Science (General); Science

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Senese, N. (2017). Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/140971

Chicago Manual of Style (16^th Edition):

Senese, Nicolas. “Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors.” 2017. Doctoral Dissertation, University of Michigan. Accessed January 15, 2021. http://hdl.handle.net/2027.42/140971.

MLA Handbook (7^th Edition):

Senese, Nicolas. “Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors.” 2017. Web. 15 Jan 2021.

Vancouver:

Senese N. Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors. [Internet] [Doctoral dissertation]. University of Michigan; 2017. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2027.42/140971.

Council of Science Editors:

Senese N. Role of Regulator of G-Protein Signaling Proteins in Serotonin and Opioid Mediated Behaviors. [Doctoral Dissertation]. University of Michigan; 2017. Available from: http://hdl.handle.net/2027.42/140971

16. Mighiu, Alexandra Sorana. Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice.

Degree: 2014, University of Toronto

URL: http://hdl.handle.net/1807/44045

►

Atrial arrhythmias are very common clinically relevant conditions that are strongly associated with aging and parasympathetic tone. Additionally, ATP-sensitive K+ (KATP) channel activation has been… (more)

Subjects/Keywords: RGS proteins; atrial arrhythmias; KATP channels; 0719

…PKA Protein Kinase A PKC Protein Kinase C RAA Right Atrial Appendage viii RGS… …activating proteins (GAPs). Regulators of G protein signaling (75;76), or RGS… …proteins, are a mammalian family of >35 GAPs for Gα subunits (77). RGS proteins are… …defined by a shared 120-130 amino acid domain (the RGS domain) that binds directly to… …x28;Figure 1-2a). Binding of RGS proteins to the activated Gα subunit can also…

9 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mighiu, A. S. (2014). Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/44045

Chicago Manual of Style (16^th Edition):

Mighiu, Alexandra Sorana. “Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice.” 2014. Masters Thesis, University of Toronto. Accessed January 15, 2021. http://hdl.handle.net/1807/44045.

MLA Handbook (7^th Edition):

Mighiu, Alexandra Sorana. “Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice.” 2014. Web. 15 Jan 2021.

Vancouver:

Mighiu AS. Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice. [Internet] [Masters thesis]. University of Toronto; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/1807/44045.

Council of Science Editors:

Mighiu AS. Mechanisms Underlying the Pathogenesis of Atrial Arrhythmias in RGS4-deficient Mice. [Masters Thesis]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/44045

University of Miami

17. Sandiford, Simone L. Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor.

Degree: PhD, Molecular and Cellular Pharmacology (Medicine), 2009, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/311

► Regulators of G protein signaling (RGS) are a diverse group of proteins, which play a fundamental role in modulation of G protein coupled receptor… (more)

▼ Regulators of G protein signaling (RGS) are a diverse group of proteins, which play a fundamental role in modulation of G protein coupled receptor signal transduction. RGS proteins are primarily known as GTPase activating proteins (GAPs) for Gá subunits. In addition to the RGS domain, which is responsible for GAP activity, most RGS proteins also contain other structural motifs. The R7 family of RGS proteins for example, which consists of RGS-6, 7, 9 and 11 gene products, also contains DEP, DHEX and GGL domains. All R7 RGS proteins are obligatory binding partners with G protein beta subunit, G beta sub five, which binds to the GGL domain. In my dissertation work, I provide insights into significance of the multi-domain architecture of G beta sub five-RGS7. I have identified a novel intramolecular interaction within the G beta sub five-RGS7 complex; between the DEP domain of RGS7 and G beta sub five subunit. My experimental evidence supports the idea that G beta sub five-RGS7 can exist in at least two hypothetical conformations: "closed" where the DEP domain and G beta sub five subunit are bound to each other, and "open" where DEP and G beta sub five are not interacting, and as a result both these proteins can associate with other binding partners. My results indicate that in its "open" conformation, G beta sub five-RGS7 can selectively inhibit calcium mobilization elicited by stimulated muscarinic acetylcholine receptor type 3 (M3R). This inhibition is mediated by direct interaction between the third intracellular loop of M3R and the DEP domain of RGS7. In addition to the effect on M3R signaling, I observed that the G beta sub five-RGS7 complex redistributes from the cytosol to endocytic vesicles in an M3R-specific manner. These results identify a novel molecular mechanism that can impart receptor-subtype selectivity on signal transduction via G protein-coupled receptors. Lastly, I have identified a small group of compounds that inhibits the DEP-G beta sub five interaction. These compounds may serve as starting points for design of G beta sub five-RGS7 modulators in the future. Advisors/Committee Members: Charles W. Luetje, Stephen D. Roper, Kerry L. Burnstein, Vladlen Z. Slepak, Alan V. Smrcka.

Subjects/Keywords: DEP Domain; Calcium; GPCRs; Signal Transduction; RGS Proteins

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sandiford, S. L. (2009). Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/311

Chicago Manual of Style (16^th Edition):

Sandiford, Simone L. “Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor.” 2009. Doctoral Dissertation, University of Miami. Accessed January 15, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/311.

MLA Handbook (7^th Edition):

Sandiford, Simone L. “Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor.” 2009. Web. 15 Jan 2021.

Vancouver:

Sandiford SL. Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor. [Internet] [Doctoral dissertation]. University of Miami; 2009. [cited 2021 Jan 15]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/311.

Council of Science Editors:

Sandiford SL. Interaction of the G Beta Sub Five-RGS7 Complex with the Muscarinic Acetylcholine M3 Receptor. [Doctoral Dissertation]. University of Miami; 2009. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/311

National University of Ireland – Galway

18. Connaughton, Eanna. Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults.

Degree: 2015, National University of Ireland – Galway

URL: http://hdl.handle.net/10379/5421

► Human blood monocytes are currently classified into three subsets: CD14++CD16- “Classical”, CD14++CD16+ “Intermediate” and CD14+CD16++ “Non-Classical”. Distinct functional differences between Classical and Non-Classical have been… (more)

▼ Human blood monocytes are currently classified into three subsets: CD14++CD16- “Classical”, CD14++CD16+ “Intermediate” and CD14+CD16++ “Non-Classical”. Distinct functional differences between Classical and Non-Classical have been described but the role of Intermediate monocytes is less clear. In profiling monocytes from healthy adults by multi-colour flow cytometry, we observed that Intermediate monocytes exhibit dichotomous surface expression of the Class II major histocompatibility protein HLA-DR, with separate sub-populations expressing mid- (DRmid) and high-levels (DRhi). Further profiling of cell surface markers demonstrated that, compared to the DRhi subset, DRmid Intermediate monocytes express higher levels of CCR2 and CD62L, and lower levels of CD45, CX3CR1, LFA-1, VLA-4 and Mac-1, indicating heterogeneity for multiple functionally-relevant proteins. We assessed how the newly described Intermediate sub-populations interact with and migrate through endothelium in in vitro assays. Results indicated both the DRmid and DRhi subsets are highly adherent to resting and activated primary human aortic endothelium, with adherence of the DRmid subset being partially mediated by CD11a. Both sub-populations exhibited poor CCL2-induced transmigration in contrast to the highly migratory CCR2+ Classical monocytes, despite the fact that DRmid and DRhi subset expressing CCR2+ and CCR2int phenotypes respectively. Further experiments revealed reduced intracellular calcium release and filamentous actin polymerisation, suggesting early termination of the CCL2-CCR2 signal. Chemokine receptors are G-protein coupled receptors (GPCRs), and GPCR signalling may be regulated by Regulator of G-Protein Signalling (RGS) proteins. We quantified mRNA levels of RGS1, 2, 12 and 18 in the monocyte subsets. Interestingly, elevated RGS1 was detected in the newly-described Intermediate monocyte subpopulations. RGS1 has been implicated as a negative regulator of CCR2 signalling in monocytes. Therefore, the results are consistent with a role for RGS1 up-regulation in the blunted CCL2-induced signalling and migration of the DRmid and DRhi intermediate monocytes. Overall, the results of this project add novel details to current knowledge regarding human Intermediate monocytes provide further evidence for heterogeneity within this monocyte subset and indicate that changes in the intracellular regulation of chemokine receptor signalling may contribute to DRmid intermediate monocyte expansion in the circulation during inflammatory disorders. Advisors/Committee Members: Griffin, Matthew (advisor), Ceredig, Rhodri (advisor).

Subjects/Keywords: Monocytes; RGS Proteins; Intermediate; CCR2; MCP-1; CCL2; HLA.DR; Intracellular Calcium; Medicine; Healthy adults; Intermediate monocytes; Regenerative Medicine Institute (REMEDI)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Connaughton, E. (2015). Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults. (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/5421

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Connaughton, Eanna. “Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults. ” 2015. Thesis, National University of Ireland – Galway. Accessed January 15, 2021. http://hdl.handle.net/10379/5421.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Connaughton, Eanna. “Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults. ” 2015. Web. 15 Jan 2021.

Vancouver:

Connaughton E. Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults. [Internet] [Thesis]. National University of Ireland – Galway; 2015. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10379/5421.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Connaughton E. Phenotypic and functional heterogeneity of intermediate monocytes in healthy adults. [Thesis]. National University of Ireland – Galway; 2015. Available from: http://hdl.handle.net/10379/5421

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Western Ontario

19. Tuomi, Jari Michael. Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse.

Degree: 2011, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/181

► Arrhythmia mechanisms rely on multiple factors including structural (myogenic), nervous (neurogenic), and interrelated (the neuro-myogenic interface) factors. I hypothesized that due to this neuro-myogenic interface,… (more)

▼ Arrhythmia mechanisms rely on multiple factors including structural (myogenic), nervous (neurogenic), and interrelated (the neuro-myogenic interface) factors. I hypothesized that due to this neuro-myogenic interface, the intrinsic cardiac autonomic nervous system (ICANS) is involved in most atrial arrhythmias. This thesis also provides a "Threshold Model" as a tool to assess the role of different physiological factors influencing arrhythmia. This model allows relative comparison and interpretation of the role of various factors influencing arrhythmogenesis. The mouse allows relatively simple manipulation of genes to determine their role in arrhythmia. This thesis determined what atrial arrhythmias are inducible in the mouse (in vivo) and how to systematically study those arrhythmias. I found that atrial tachycardia/fibrillation (AT/F) and junctional tachycardia (JT) are inducible in the mouse. AF and JT pose significant clinical challenges as many patients do not respond well to current interventions. Neurogenic AF relies on acetylcholine, while myogenic AF relies, in part on gap junctions formed by connexins (Cxs). The atria has muscarinic M2 and M3 receptors. The duration of M2R/M3R G protein signalling is regulated by GTP hydrolysis, a process accelerated by the regulators of G protein signalling (RGS). RGS2 deficient (RGS2-/-) mice had reduced refractory periods that were normalized with a selective M3R blocker (Darifenacin) and increased susceptibility to AT/F induction compared to littermates. For the first time, this showed a role of M3 and RGS in atrial arrhythmia. Cx40 deficient (Cx40-/-) mice were protected from carbachol induced AT/F, while Cx43 G60S mutant (Cx43G60S/+) mice, with an 80% reduction in phospho-Cx43 in the atria were highly susceptible to AT/F that was terminated by darifenacin. This shows a novel neurogenic component to what was previously described as myogenic arrhythmia. Another novel finding was that JT has a neurogenic component, resulting from inappropriate AV nodal pacemaker activation initiated by autonomics. Ivabradine hydrochloride, a selective pacemaker channel blocker, prevented JT and may be useful in patients with JT. In conclusion, this thesis has provided novel findings of the vital role of the neuro-myogenic interface in atrial arrhythmias and has provided the basis for future investigations of potential therapeutic options for patients.

Subjects/Keywords: atrial arrhythmia; atrial fibrillation; junctional tachycardia; mouse electrophysiology; RGS proteins; Gap Junctions; Circulatory and Respiratory Physiology; Physiological Processes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tuomi, J. M. (2011). Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tuomi, Jari Michael. “Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse.” 2011. Thesis, University of Western Ontario. Accessed January 15, 2021. https://ir.lib.uwo.ca/etd/181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tuomi, Jari Michael. “Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse.” 2011. Web. 15 Jan 2021.

Vancouver:

Tuomi JM. Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse. [Internet] [Thesis]. University of Western Ontario; 2011. [cited 2021 Jan 15]. Available from: https://ir.lib.uwo.ca/etd/181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tuomi JM. Mechanisms of Atrial Arrhythmia: Investigations of the Neuro-Myogenic Interface in the Mouse. [Thesis]. University of Western Ontario; 2011. Available from: https://ir.lib.uwo.ca/etd/181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

20. Turner, Kathryn Lisa. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/25339

► Lysophosphatidic acid (LPA) is a signaling molecule that induces survival, metastasis, migration, and proliferation in ovarian cancer cells by binding to G-protein coupled receptors (GPCRs),… (more)

Subjects/Keywords: LPA; Lysophosphatidic acid; Ovarian cancer; SKOV-3 cells; RGS; Regulator of G-protein signaling; G-protein; cAMP; Migration; RGS2; RGS19

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Turner, K. L. (2014). Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/25339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Turner, Kathryn Lisa. “Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.” 2014. Thesis, University of Georgia. Accessed January 15, 2021. http://hdl.handle.net/10724/25339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Turner, Kathryn Lisa. “Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells.” 2014. Web. 15 Jan 2021.

Vancouver:

Turner KL. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10724/25339.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Turner KL. Inhibition of LPA signaling pathways by RGS protein overexpression in ovarian cancer cells. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/25339

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Michigan

21. Lan, Keng-Li. Mechanism and specificity of G protein regulation by RGS proteins.

Degree: PhD, Pure Sciences, 1999, University of Michigan

URL: http://hdl.handle.net/2027.42/131700

► Many extracellular stimuli convey information to cells through G protein-coupled receptors. Steady state activation of this pathway depends on GTPase activity of the Galpha subunit.… (more)

▼ Many extracellular stimuli convey information to cells through G protein-coupled receptors. Steady state activation of this pathway depends on GTPase activity of the Galpha subunit. Three advances in G protein function are addressed in this thesis: (1) The roles of tryptophans in fluorescent and functional properties of Galphao; (2) Rapid kinetics of RGS-mediated Galpha deactivation and (3) characterization of the RGS-insensitive Galpha mutants. Fluorescence of two mutant Galphao proteins (W132F and W212F) were examined to understand the determinants of the N-methyl-3^'- O-anthraniloyl (Mant)-guanine nucleotide fluorescence signals. Trp212 in Galphao is essential for GTP-stimulated fluorescence, whereas resonance energy transfer from both Trp132 and Trp212 contributes to the enhanced Mant-guanine nucleotide fluorescence upon binding to Galphao. R&barbelow;egulator of G&barbelow; protein s&barbelow;ignaling (RGS) proteins function as GTPase activating proteins (GAPs) for Galpha and are thought to be responsible for rapid deactivation of G protein responses. Using stopped-flow spectrofluorimetry, I examined G protein deactivation on the millisecond time scale. RGS4 dramatically enhanced deactivation rates of Galphao and Galphai1. The rate increased linearly with RGS concentration to over 5 sec^-1. These are the first in vitro measurements of G protein deactivation at rates comparable to in vivo turn-off of G-protein-mediated signals. In contrast to the rapid deactivation of Galpha when GTP was bound, Mant-GTP-bound Galphao was not deactivated rapidly by RGS4, suggesting that Mant-GTP prevents RGS regulation. Therefore, Mant-GTP may be a useful tool to generate active but RGS-insensitive Galpha to study the physiological role of RGS. G protein alpha subunit mutants insensitive to RGS proteins could be used to assess the combined role of all RGS proteins in the function of that subunit in vivo. Based on a yeast Galpha mutation, a single glycine residue was mutated to serine in Galphao or Galphai1. RGS4 and RGS7 were unable to stimulate GTP hydrolysis by the G > S mutant proteins. The ability of G183S Galphai1 to interact with receptor, Gbetagamma and adenylyl cyclase was similar to that wild type, however, the affinity for RGS4 was decreased >1000-fold. The G > S mutants will be useful in biochemical or expression studies to evaluate the role of endogenous RGS proteins in Galphai function. Advisors/Committee Members: Neubig, Richard R. (advisor).

Subjects/Keywords: Alpha; Deactivation; G Protein; Mant Gtp; Mechanism; Regulation; Rgs Proteins; Specificity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lan, K. (1999). Mechanism and specificity of G protein regulation by RGS proteins. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/131700

Chicago Manual of Style (16^th Edition):

Lan, Keng-Li. “Mechanism and specificity of G protein regulation by RGS proteins.” 1999. Doctoral Dissertation, University of Michigan. Accessed January 15, 2021. http://hdl.handle.net/2027.42/131700.

MLA Handbook (7^th Edition):

Lan, Keng-Li. “Mechanism and specificity of G protein regulation by RGS proteins.” 1999. Web. 15 Jan 2021.

Vancouver:

Lan K. Mechanism and specificity of G protein regulation by RGS proteins. [Internet] [Doctoral dissertation]. University of Michigan; 1999. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2027.42/131700.

Council of Science Editors:

Lan K. Mechanism and specificity of G protein regulation by RGS proteins. [Doctoral Dissertation]. University of Michigan; 1999. Available from: http://hdl.handle.net/2027.42/131700

University of Michigan

22. Fu, Ying. The role of endogenous RGS proteins in regulation of cardiac automaticity.

Degree: PhD, Pharmacology, 2007, University of Michigan

URL: http://hdl.handle.net/2027.42/126420

► Regulator of G protein Signaling (RGS) proteins modulate G protein-mediated signaling by accelerating the GTPase activity of Galpha subunits, thereby shortening the lifetime of active… (more)

▼ Regulator of G protein Signaling (RGS) proteins modulate G protein-mediated signaling by accelerating the GTPase activity of Galpha subunits, thereby shortening the lifetime of active signaling molecules, i.e. Galpha-GTP and free Gbetagamma complexes. Despite extensive studies for a decade, our understanding of the physiological functions of RGS proteins is still in its infancy. The lack of pharmacological inhibitors for RGS proteins and functional redundancy among multiple family members (>30) imposes tremendous challenges for the application of antisense or genetic knockout strategies in assessing the role of RGS proteins in physiological processes. Moreover, another level of complexity lies in the interaction of RGS proteins and multiple isoforms of G proteins. Therefore, we employed RGS-insensitive mutations (RGSi) in Galpha subunits that disrupt the Galpha-RGS interaction and introduced them into embryonic stem (ES) cells by homologous recombination. This approach allowed me to study the role of endogenous RGS proteins as a class in a Galpha isoform-specific manner without alterations in expression of mutant proteins. Cardiac automaticity was examined in spontaneously contracting ES cell-derived cardiocytes (ESDC) in vitro, in an isolated heart perfusion system, and in vivo in intact animals. I demonstrate that endogenous RGS proteins potently modulate the chronotropic control by adenosine A, and muscarinic M2 receptors, which differentially utilize Galpha_o and Galpha_i2 and associated downstream effectors. The G-protein-coupled inward rectifying K⁺ currents are strongly modulated by RGS proteins and play an essential role in M₂ receptor-induced bradycardia, whereas A₁, receptors seem to preferentially couple to Galpha_o and other downstream effectors. Telemetry recording in conscious, unrestrained mice revealed hyperactivity, disrupted thermoregulation, and enhanced basal cardiac function, which strongly suggest alterations in the central nervous system (CNS) of Galpha_i2RGSi mutant mice. Using an isolated heart perfusion system, I confirmed that RGS proteins modulate intrinsic cardiac automaticity independent of CNS and vascular inputs. Furthermore, enhanced Galpha_i2 signaling by blocking RGS actions also results in the development of atrioventricular block. Thus, endogenous RGS proteins play an important role in regulation of cardiovascular and neurobehavioral function and may also be implicated in pathophysiological processes. Advisors/Committee Members: Neubig, Richard Robert (advisor).

Subjects/Keywords: Cardiac Automaticity; Endogenous; G Proteins; G-proteins; Regulation; Rgs Proteins; Role

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fu, Y. (2007). The role of endogenous RGS proteins in regulation of cardiac automaticity. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/126420

Chicago Manual of Style (16^th Edition):

Fu, Ying. “The role of endogenous RGS proteins in regulation of cardiac automaticity.” 2007. Doctoral Dissertation, University of Michigan. Accessed January 15, 2021. http://hdl.handle.net/2027.42/126420.

MLA Handbook (7^th Edition):

Fu, Ying. “The role of endogenous RGS proteins in regulation of cardiac automaticity.” 2007. Web. 15 Jan 2021.

Vancouver:

Fu Y. The role of endogenous RGS proteins in regulation of cardiac automaticity. [Internet] [Doctoral dissertation]. University of Michigan; 2007. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/2027.42/126420.

Council of Science Editors:

Fu Y. The role of endogenous RGS proteins in regulation of cardiac automaticity. [Doctoral Dissertation]. University of Michigan; 2007. Available from: http://hdl.handle.net/2027.42/126420

23. Mohammadiarani, Hossein. SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS.

Degree: PhD, 2017, University of New Hampshire

URL: https://scholars.unh.edu/dissertation/2303

► I used molecular dynamics (MD) simulations as a primary tool to study folding and dynamics of signaling and regulatory proteins. Specifically, I have studied two… (more)

▼ I used molecular dynamics (MD) simulations as a primary tool to study folding and dynamics of signaling and regulatory proteins. Specifically, I have studied two classes of proteins: the first part of my thesis reports studies on peptides and receptors of the insulin family, and the second part reports on studies of regulatory proteins from the G-protein coupled receptor family. The first problem that I investigated was understanding the folding mechanism of the insulin B-chain and its mimetic peptide (S371) which were studied using enhanced sampling simulation methods. I validated our simulation approaches by predicting the known solution structure of the insulin B-chain helix and then applied them to study the folding of the mimetic peptide S371. Potentials of mean force (PMFs) along the reaction coordinate for each peptide are further resolved using the metadynamics method. I further proposed receptor-bound models of S371 that provide mechanistic explanations for competing binding properties of S371 and a tandem hormone-binding element of the receptor known as the C-terminal (CT) peptide. Next, I studied the all-atom structural models of peptides containing 51 residues from the transmembrane regions of IR and the type-1 insulin-like growth factor receptor (IGF1R) in a lipid membrane. In these models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C-terminal residues corresponding to the juxta-membrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. I also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane-solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane-solvent interfaces. The metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. I further studied dimerization propensities of IR transmembrane domains using three different constructs in a lipid bilayer (isolated helices, ectodomain-anchored helices, and kinase-anchored helices). These studies revealed that the transmembrane domains can dimerize in isolation and in kinase-anchored forms, but not significantly in the ectodomain construct. The final studies in my thesis are focused on interplay of protein dynamics and small-molecule inhibition in a set of regulatory proteins known as the Regulators of G-protein Signaling (RGS) proteins. Thiadiazolidinone (TDZD) compounds have been shown to inhibit the protein-protein interaction between RGS and the alpha subunit of G-proteins by covalent modification of cysteine residues in RGS… Advisors/Committee Members: Harish Vashisth, Russell T. Carr, Kang Wu.

Subjects/Keywords: Hydrogen-deuterium exchange (HDX); Insulin hormone; Insulin receptor; Molecular dynamics (MD); Protein and peptide folding; Regulator of G-protein signaling (RGS); Molecular biology; Computational chemistry; Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mohammadiarani, H. (2017). SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS. (Doctoral Dissertation). University of New Hampshire. Retrieved from https://scholars.unh.edu/dissertation/2303

Chicago Manual of Style (16^th Edition):

Mohammadiarani, Hossein. “SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS.” 2017. Doctoral Dissertation, University of New Hampshire. Accessed January 15, 2021. https://scholars.unh.edu/dissertation/2303.

MLA Handbook (7^th Edition):

Mohammadiarani, Hossein. “SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS.” 2017. Web. 15 Jan 2021.

Vancouver:

Mohammadiarani H. SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS. [Internet] [Doctoral dissertation]. University of New Hampshire; 2017. [cited 2021 Jan 15]. Available from: https://scholars.unh.edu/dissertation/2303.

Council of Science Editors:

Mohammadiarani H. SIMULATION STUDIES OF SIGNALING AND REGULATORY PROTEINS. [Doctoral Dissertation]. University of New Hampshire; 2017. Available from: https://scholars.unh.edu/dissertation/2303

Indian Institute of Science

24. Pramod, K K. Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L.

Degree: PhD, Faculty of Science, 2011, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/1143

Subjects/Keywords: Datura Metel; cDNA; Deoxy Nuclaic Acid; rgs-CaM; Biochemical Genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pramod, K. K. (2011). Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/1143

Chicago Manual of Style (16^th Edition):

Pramod, K K. “Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L.” 2011. Doctoral Dissertation, Indian Institute of Science. Accessed January 15, 2021. http://etd.iisc.ac.in/handle/2005/1143.

MLA Handbook (7^th Edition):

Pramod, K K. “Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L.” 2011. Web. 15 Jan 2021.

Vancouver:

Pramod KK. Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2011. [cited 2021 Jan 15]. Available from: http://etd.iisc.ac.in/handle/2005/1143.

Council of Science Editors:

Pramod KK. Molecular Cloning And Characterization Of Two Tropane Alkaloid Biosynthetic Enzyme cDNAs And Studies On rgs-CaM Like Gene In Datura Metel L. [Doctoral Dissertation]. Indian Institute of Science; 2011. Available from: http://etd.iisc.ac.in/handle/2005/1143

25. Anderson, Garret R. Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum.

Degree: PhD, 2010, University of Minnesota

URL: http://purl.umn.edu/59525

► G protein-coupled receptor (GPCR) signaling pathways mediate the transmission of signals from the extracellular environment to the generation of cellular responses, a process that is… (more)

▼ G protein-coupled receptor (GPCR) signaling pathways mediate the transmission of signals from the extracellular environment to the generation of cellular responses, a process that is critically important for neurons and neurotransmitter action. The ability to promptly respond to rapidly changing stimulation requires timely inactivation of G proteins, a process controlled by a family of specialized proteins known as regulators of G protein signaling (RGS). The R7 group of RGS proteins (R7 RGS) has received special attention due to their pivotal roles in the regulation of a range of crucial neuronal processes such as vision, motor control, reward behavior and nociception in mammals. One member of the R7 RGS family, RGS9-2 has been previously implicated as an essential modulator of signaling through neuronal dopamine and opioid G protein coupled receptors. RGS9-2 is specifically expressed in striatal neurons where it forms complexes with R7BP (R7 RGS Binding Protein), which we have found to ultimately affect several critical properties of RGS9-2. First, it is this interaction with R7BP which is necessary for determining the subcellular targeting of RGS9-2 to the plasma membrane and to the specialized neuronal compartment of excitatory synapses, the postsynaptic density. Secondly, R7BP plays a selective role amongst the R7 RGS family in determining the proteolytic stability of RGS9-2. Further characterization of R7 RGS complexes in the striatum revealed that two equally abundant R7 RGS proteins, RGS9-2 and RGS7, are unequally coupled to the R7BP subunit which is present in complex predominantly with RGS9-2 rather than with RGS7. However, upon changes in neuronal activity the subunit composition of these complexes in the striatum undergoes rapid and extensive remodeling. Changes in the neuronal excitability or oxygenation status result in extracellular calcium entry, uncoupling RGS9-2 from R7BP, triggering its selective degradation. Concurrently, released R7BP binds to cytoplasmic RGS7 and recruits it to the plasma membrane and the postsynaptic density. These observations introduce activity dependent remodeling of R7 RGS complexes as a new molecular plasticity mechanism in striatal neurons and suggest a general model for achieving rapid posttranslational subunit rearrangement in multi-subunit complexes. The physiological consequence of this remodeling process appears to play a role in determining the signaling sensitivity to dopamine stimulation. Considering that upon the genetic elimination of RGS9, all available R7BP is funneled towards complex formation with RGS7, not only are RGS9 controlled GPCR signaling pathways affected, but those controlled by RGS7 as well. RGS9 knockout mice have an increased sensitivity to dopamine and opioid receptor stimulation and consequently display altered motor and reward behavior. The question arises as to the role of modulation of RGS7 function in controlling these behaviors. Since the function of RGS9-2 is controlled by its association with R7BP, we would predict that the…

Subjects/Keywords: Dopamine; GPCR; Macromolecular complexes; Opioid; Protein Degradation; RGS; Pharmacology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Anderson, G. R. (2010). Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/59525

Chicago Manual of Style (16^th Edition):

Anderson, Garret R. “Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum.” 2010. Doctoral Dissertation, University of Minnesota. Accessed January 15, 2021. http://purl.umn.edu/59525.

MLA Handbook (7^th Edition):

Anderson, Garret R. “Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum.” 2010. Web. 15 Jan 2021.

Vancouver:

Anderson GR. Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum. [Internet] [Doctoral dissertation]. University of Minnesota; 2010. [cited 2021 Jan 15]. Available from: http://purl.umn.edu/59525.

Council of Science Editors:

Anderson GR. Dynamic regulation of R7BP (R7 Binding Protein) containing R7 RGS (R7 Regulators of G protein Signaling) protein complexes: role in controlling neuronal dopamine and opioid signaling in the striatum. [Doctoral Dissertation]. University of Minnesota; 2010. Available from: http://purl.umn.edu/59525

26. Posokhova, Ekaterina N. Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners.

Degree: PhD, Pharmacology, 2012, University of Minnesota

URL: http://purl.umn.edu/143602

► G Protein Coupled Receptor (GPCR) signaling pathways convert signals from the extracellular environment into cellular responses, which is critically important for neurotransmitter action both in… (more)

▼ G Protein Coupled Receptor (GPCR) signaling pathways convert signals from the extracellular environment into cellular responses, which is critically important for neurotransmitter action both in central and peripheral nervous systems. The ability to promptly respond to rapidly changing stimulation requires timely inactivation of G proteins, a process controlled by a family of specialized proteins known as Regulators of G protein Signaling (RGS). The R7 group of RGS proteins (R7 RGS) has received special attention due to pivotal roles in the regulation of a range of crucial neuronal processes such as vision, motor control, reward behavior, and nociception in mammals. One member of R7 RGS family, RGS9-2 has been previously implicated as a key regulator of dopamine and opioid signaling pathways in the basal ganglia of the brain, where it mediates motor control and reward behavior. Dynamic association of RGS9-2 with R7BP (R7 family Binding Protein) is critically important for the regulation of RGS9-2 expression level by proteolytic mechanisms. Changes in RGS9-2 expression are observed in response to a number of signaling events and are thought to contribute to the plasticity of the neurotransmitter action. To unravel the molecular mechanisms regulating levels of RGS9-2 upon its dissociation from R7BP we developed a novel application of the quantitative proteomics approach to monitor interactome dynamics of RGS9-2 in mice. We show that a molecular chaperone HSC70 (Heat Shock Cognate protein 70) identified by this approach is a critical regulator of RGS9-2 expression. HSC70 binds the intrinsically disordered C-terminal domain of RGS9-2 upon the dissociation of R7BP/RGS9-2 complex, and targets the complex to degradation. In addition to their critical role in shaping neurotransmitter response in the brain, RGS proteins can regulate function of peripheral organs by modulating their responses to the influences of autonomic nervous system. The role of RGS proteins in the regulation of cardiac function and heart rate has received significant attention in the recent years. With over 30 RGS proteins identified, their specific roles in heart physiology remain to be established. Parasympathetic autonomic influence plays an important role in shaping cardiac output acting to decrease heart rate and counteract the pro-arrhythmic effects of sympathetic activation. Acetylcholine (ACh) released from post-ganglionic parasympathetic neurons activates M2 muscarinic receptor (M2R) and its downstream effector, potassium channel IKACh, in pacemaker cells and atrial myocytes. This leads to cell hyperpolarization and ultimately, decreased heart rate (HR). The second part of the dissertation demonstrates cardiac expression of RGS6 member of R7 RGS family, which has been previously thought to be a neuron-specific regulator. Elimination of RGS6 in mice results in potentiated M2R-IKACh signaling, as evidenced by prolonged deactivation kinetics of IKACh in cardiomyocytes, mild resting bradycardia, and augmented HR deceleration in response to…

Subjects/Keywords: Chaperone; G protein; Heart rate; Interactome; parasympathetic; RGS

…86 vi List of Tables Table 1. Interactions of R7 RGS proteins outside of the complexes… …vii List of Figures Figure 1.1: Organization of trimeric complexes between R7 RGS… …postsynaptic density PVDF – polyvinylidene fluoride R7BP – R7 RGS binding protein R9AP – RGS9 anchor… …protein RGS – regulator of G protein signaling RNA - ribonucleic acid ROS – rod outer segment S… …Published Manuscripts 1. Anderson G.R., Posokhova E.N., Martemyanov K.A. The R7 RGS protein family…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Posokhova, E. N. (2012). Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners. (Doctoral Dissertation). University of Minnesota. Retrieved from http://purl.umn.edu/143602

Chicago Manual of Style (16^th Edition):

Posokhova, Ekaterina N. “Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners.” 2012. Doctoral Dissertation, University of Minnesota. Accessed January 15, 2021. http://purl.umn.edu/143602.

MLA Handbook (7^th Edition):

Posokhova, Ekaterina N. “Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners.” 2012. Web. 15 Jan 2021.

Vancouver:

Posokhova EN. Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners. [Internet] [Doctoral dissertation]. University of Minnesota; 2012. [cited 2021 Jan 15]. Available from: http://purl.umn.edu/143602.

Council of Science Editors:

Posokhova EN. Molecular mechanisms regulating G protein signaling in brain and heart: role of R7 RGS proteins and their binding partners. [Doctoral Dissertation]. University of Minnesota; 2012. Available from: http://purl.umn.edu/143602

27. Cain, Matthew D. Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision.

Degree: PhD, Biology and Biomedical Sciences: Molecular Cell Biology, 2014, Washington University in St. Louis

URL: https://openscholarship.wustl.edu/etd/1288

► ABSTRACT OF THE DISSERTATION Characterization of the Role of RGS7-family Proteins in Mammalian Retina and Vision by Matthew David Cain Doctor of Philosophy in… (more)

▼ ABSTRACT OF THE DISSERTATION Characterization of the Role of RGS7-family Proteins in Mammalian Retina and Vision by Matthew David Cain Doctor of Philosophy in Biology and Biomedical Sciences Molecular Cell Biology Washington University in St. Louis, 2014 Professor Kendall J. Blumer, Chairperson GPCR/G protein signaling is a critical component of neuronal signal transduction and function. G protein signaling is regulated by a family of regulator of G protein signaling (RGS) proteins that act as GTPase activating proteins (GAPs) for Gα subunits. In the retina, the R7-RGS family of RGS proteins which specifically act as GAPs toward Gi/o, are critical regulators of phototransduction and ON bipolar cell light responses in the outer retina. While R7-RGS proteins are expressed throughout the inner retina, their function there is unknown. The goal of this dissertation project is to characterize R7-RGS regulation on retina function and vision. This dissertation is divided into four parts: i) analysis of inner retinal function in mature and developing R7BP^-/- retinas, ii) characterization of composition and localization of R7-RGS/R7BP complexes in the dorsal lateral geniculate nucleus (dLGN), iii) characterization of blockade of RGS regulation of Gi2 and Go subunits on outer retina function, and iv) preliminary analysis of the effect of RGS6 ablation on vision. In part i), we found that R7BP is expressed in starburst amacrine cells (SAC) and retinal ganglion cells (RGC). R7BP regulates mesopic RGC light responses and glutamatergic wave burst duration in mature and developing retina, respectively. In part ii), we found that R7PB is expressed in the dLGN. R7BP interacts with RGS6 and RGS7 in lateral geniculate nucleus lysates, but is not necessary for their membrane localization. In part iii), outer retinal phenotypes of RGS-insensitive Gi2 and Go mutant mice were characterized. RGS regulation of Gi2 is necessary for normal rod light responses. Heterozygous expression of RGS-insensitive Go subunits was not sufficient to perturb ON bipolar cell light responses or dendritic morphology. In part iv), we found that RGS6 is expressed in starburst amacrine cells. RGS6 localization to SAC plexi is independent of R7BP. We demonstrated that, although dispensable for normal phototransduction or ON bipolar light responses, RGS6 is necessary for normal spatial vision. Based on these findings, we suggest that RGS regulation of Gi/o signaling is necessary for normal retinal function and that R7-RGS proteins regulate inner retinal function. Additionally, we identified several new candidate circuits to further explore R7-RGS function in the visual system. Advisors/Committee Members: Kendall J Blumer.

Subjects/Keywords: dLGN; ERG; G protein signaling; retina; retinal wave; RGS

…G protein signaling is regulated by a family of regulator of G protein signaling (RGS… …the retina, the R7RGS family of RGS proteins which specifically act as GAPs toward Gi/o, are… …While R7-RGS proteins are expressed throughout the inner retina, their function there is… …unknown. The goal of this dissertation project is to characterize R7-RGS regulation on retina… …dLGN), iii) characterization of blockade of RGS regulation of Gi2 and Go subunits…

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APA (6^th Edition):

Cain, M. D. (2014). Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/1288

Chicago Manual of Style (16^th Edition):

Cain, Matthew D. “Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision.” 2014. Doctoral Dissertation, Washington University in St. Louis. Accessed January 15, 2021. https://openscholarship.wustl.edu/etd/1288.

MLA Handbook (7^th Edition):

Cain, Matthew D. “Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision.” 2014. Web. 15 Jan 2021.

Vancouver:

Cain MD. Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2014. [cited 2021 Jan 15]. Available from: https://openscholarship.wustl.edu/etd/1288.

Council of Science Editors:

Cain MD. Characterization of the Role of R7-RGS Proteins in Mammalian Retina and Vision. [Doctoral Dissertation]. Washington University in St. Louis; 2014. Available from: https://openscholarship.wustl.edu/etd/1288

University of Georgia

28. Baker, Lorina Gale. Molecular genetic analysis of germination and sporulation in two obligate phytopathogens.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/22295

► Two obligate fungal phytopathogens, Cronartium quercuum f. sp. fusiforme and Ustilago maydis were used to study how obligate pathogens sense and respond to host stimuli.… (more)

▼ Two obligate fungal phytopathogens, Cronartium quercuum f. sp. fusiforme and Ustilago maydis were used to study how obligate pathogens sense and respond to host stimuli. Depending upon the surface where C. q. fusiforme basidiospores alight on, they germinate directly by sending out a long thin germ tube or indirectly by sending out a short thick germ tube and producing a secondary basidiospore. I altered surface hydrophilicities to test if this characteristic affected the germination response of C. q. fusiforme basidiospores. I found that altered surface hydrophilicity did have an affect on the basidiospore germination fate and that there was a critical threshold between 42% and 54% surface wettability where C. q. fusiforme basidiospores switched germination type. To ascertain what genes are involved in the different germination types, two expression libraries enriched for genes expressed during direct or indirect germination were made. The combined expression libraries contained one hundred and eighty unique cDNAs of which fourteen were differentially expressed between the two germination states. Proteins represented by the genes within the expression libraries may be determinants of the basidiospores’ response to a favorable substrate or environment. The second part of my dissertation focuses on how obligate phytopathogens, such as Ustilago maydis, switch from in planta vegetative growth to reproductive growth. I identified three genes encoding putative regulators of G-protein signaling rgs1, rgs2, and rgs3 that could be involved in the switch from vegetative growth to sporulation. Deletion of rgs1 resulted in hyphal growth on minimal medium agar, reduced pathogenicity, and reduced in planta sporulation. I determined that the hyphal growth phenotype was due to the rgs1 strain’s inability to deactivate the G± subunits, Gpa1 and Gpa4. This suggested that both Gpa1 or Gpa4 are negative regulators of in planta sporulation. This was verified using a sporulation time course experiment where I found that the deletion of gpa1 and gpa4 caused hyper-sporulation in planta. The combined data supports a model where multiple pathways control of in planta sporulation and that under the appropriate conditions Rgs1 regulates these pathways.

Subjects/Keywords: Cronartium quercuum f. sp. fusiforme; Ustilago maydis; Obligate phytopathogen; fungi; Basidiomycete; surface wettabilities; basidiospore germination; in planta sporulation; Rgs1; Ga subunit; RGS; Gpa1; Gpa4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Baker, L. G. (2014). Molecular genetic analysis of germination and sporulation in two obligate phytopathogens. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/22295

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Baker, Lorina Gale. “Molecular genetic analysis of germination and sporulation in two obligate phytopathogens.” 2014. Thesis, University of Georgia. Accessed January 15, 2021. http://hdl.handle.net/10724/22295.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Baker, Lorina Gale. “Molecular genetic analysis of germination and sporulation in two obligate phytopathogens.” 2014. Web. 15 Jan 2021.

Vancouver:

Baker LG. Molecular genetic analysis of germination and sporulation in two obligate phytopathogens. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10724/22295.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Baker LG. Molecular genetic analysis of germination and sporulation in two obligate phytopathogens. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/22295

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

29. Callihan, Charles Phillip. The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/28214

► GPCRs are transmembrane proteins that mediate cellular responses to a wide-range of molecules by transmitting signals through intracellular heterotrimeric G-proteins. Through these G-proteins, GPCRs regulate… (more)

▼ GPCRs are transmembrane proteins that mediate cellular responses to a wide-range of molecules by transmitting signals through intracellular heterotrimeric G-proteins. Through these G-proteins, GPCRs regulate the development and physiology of numerous systems in the human body, and are implicated in many human diseases. The lysophospholipids lysophoshphatidic acid (LPA) and sphingosine 1-phosphate (S1P) activate a family of GPCRs to regulate cell growth and differentiation. This dissertation will focus on lysophospholipid signaling in ovarian cancer, stem cell pluripotency, and neural progenitor cells. Ligand binding to GPCRs induces the exchange of GDP for GTP on the Gα-subunit of the heterotrimeric G-protein, resulting in the activation of downstream signaling pathways. G-protein signaling is terminated through the action of Regulators of G-Protein Signaling (RGS) proteins. Numerous members of the RGS protein family have been implicated in various types of cancer. Our lab has shown that endogenous RGS proteins regulate LPA receptor signaling in ovarian cancer cells, and a number of RGS proteins are downregulated in chemo-resistant ovarian cancer. The studies described herein test the ability of specific RGS proteins to regulate cell survival signaling in ovarian cancer cells. Our results show that RGS10 inhibits AKT survival signaling pathways downstream of LPA. LPA and S1P are also important regulators of neural tube closure and neuronal differentiation, but the molecular details of this regulation remain undefined. Using human embryonic stem cell derived neuroepithelial progenitor (hES-NEP) cells, we have defined general mechanisms of LPA and S1P signaling in neural progenitors. Our studies show that exposure to the mycotoxin FB1 results in preferential increases in dihydrosphingosine over sphingosine, and that their receptor active 1-phosphate metabolites, dhS1P and S1P, display distinct pharmacology in hES-NEP cells. Finally, we found that LPA and S1P suppress neuronal differentiation of hES-NEP cells and enhance survival. Our results indicate that this suppression is due to LPA/S1P activation of Erk, and inhibition of AKT signaling pathways, with distinct roles for distinct receptor subtypes.

Subjects/Keywords: Lysophospholipid; Lysophoshphatidic acid; Sphingosine 1-phosphate; Dihydrosphingosine 1-phosphate; G protein coupled receptor; RGS protein; Ovarian cancer; Neural progenitor cells; Neural development; Neuronal differentiation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Callihan, C. P. (2014). The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/28214

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Callihan, Charles Phillip. “The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells.” 2014. Thesis, University of Georgia. Accessed January 15, 2021. http://hdl.handle.net/10724/28214.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Callihan, Charles Phillip. “The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells.” 2014. Web. 15 Jan 2021.

Vancouver:

Callihan CP. The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 15]. Available from: http://hdl.handle.net/10724/28214.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Callihan CP. The molecular pharmacology of lysophosphatidic acid and sphingosine 1-phosphate receptors in ovarian cancer and human neural progenitor cells. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/28214

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Han, Jing. ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION.

Degree: PhD, Neurosciences, 2007, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706

► RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates Gi/o as well… (more)

Subjects/Keywords: Biology, Neuroscience; RGS2; serotonergic; neurons; Gi/o; serotonergic neurons; RGS; PROTEIN

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Han, J. (2007). ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706

Chicago Manual of Style (16^th Edition):

Han, Jing. “ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION.” 2007. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed January 15, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706.

MLA Handbook (7^th Edition):

Han, Jing. “ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION.” 2007. Web. 15 Jan 2021.

Vancouver:

Han J. ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2007. [cited 2021 Jan 15]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706.

Council of Science Editors:

Han J. ROLE OF THE REGULATOR OF G PROTEIN SIGNALING 2 (RGS2) FOR NEURONAL AND SYSTEM FUNCTION. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1175703706

Open Access Theses and Dissertations