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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Theibert, Anne Burton <br>"). Showing records 1 – 2 of 2 total matches.

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1. Grabski, Robert. Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic.

Degree: PhD, 2008, University of Alabama – Birmingham

Metazoan cells are characterized with elaborate network of intracellular membranous compartments. These membranes allow the cell to spatially separate antagonistic processes and environments, and maintain sequential order of reactions necessary for maturation and secretion of biosynthetic cargo. The core transport machinery consists of coat proteins, tethering factors, SNAREs and small Ras-like GTPases. We have explored the function of the tethering factor p115 in organellogenesis and in secretory traffic. The p115-depleted system was utilized to explore structurefunction relationships within p115. Here, we analyzed the architecture of the Golgi after RNAi induced depletion of p115. We show that in p115 depleted cells Golgi disrupts in to dynamic perinuclear structures that retain the cis-trans polarity of the normal Golgi complex, and can reassemble after treatment with Brefeldin A and subsequent washout. We also characterized the impact of p115 depletion on the traffic and secretion of biosynthetic cargo. Our studies revealed that p115 depletion has a selective effect on cargo traffic - we observed ER retention of transmembrane VSV-G protein with no effect on trafficking of soluble proteins. The p115 tethering factor does not appear to have an enzymatic activity and acts through the interaction with its binding partners. The C-terminal coiled-coil region of p115 is critical for binding to Rab1 GTPase and SNAREs, and has been shown to be essential for p115 function in Golgi biogenesis. We used p115 deletion mutant to analyze the importance of CC3 and CC4 for p115 function. Expression of the p115/1-766 mutant, lacking CC3-4 region, in p115 depleted cells or in control cells disrupted Golgi in to scattered punctate fragments, which suggest a dominant-negative nature of the mutant. Interestingly, the p115/1-766 mutant supported ER exit of transmembrane VSV-G but arrested it in dispersed punctuate structures, without any detectable effect on transport of soluble cargo. Our studies provide the first evidence that the CC3-4 region is necessary for the function of p115. Combining our findings with the current knowledge on p115 functional domains, we propose a model where p115 not only increases the fidelity of SNARE-pin formation, but also functions in proteins sorting during ER exit of cargo proteins.

xi, 86 p. : ill., digital, PDF file

Cell Biology

Joint Health Sciences

p115 Golgi vesicular traffic

UNRESTRICTED

Advisors/Committee Members: Sztul, Elizabeth, Theibert, Anne Burton <br>, Collawn, Jim <br>, Kirk, Kevin L. <br>, Rayner, Julian C..

Subjects/Keywords: Carrier Proteins  – metabolism <; br>; Golgi Apparatus  – metabolism <; br>; Membrane Proteins  – metabolism <; br>; Protein Transport <; br>; RNA Interference

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

APA (6th Edition):

Grabski, R. (2008). Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,328

Chicago Manual of Style (16th Edition):

Grabski, Robert. “Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic.” 2008. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 16, 2019. http://contentdm.mhsl.uab.edu/u?/etd,328.

MLA Handbook (7th Edition):

Grabski, Robert. “Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic.” 2008. Web. 16 Nov 2019.

Vancouver:

Grabski R. Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2008. [cited 2019 Nov 16]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,328.

Council of Science Editors:

Grabski R. Using RNA interference to study the function of the tethering protein p115 in ER-Golgi traffic. [Doctoral Dissertation]. University of Alabama – Birmingham; 2008. Available from: http://contentdm.mhsl.uab.edu/u?/etd,328

2. Tower-Gilchrist, Cristy (Cristy Davette). The role of protein folding and protein trafficking in human disease.

Degree: PhD, 2011, University of Alabama – Birmingham

Project 1: Expansion of CAG repeats encoding glutamine in huntingtin and ataxin 3 causes the neurodegenerative diseases Huntington's disease (HD) and spinocerebellar ataxia 3 (SCA3), respectively. Both poly-glutamine (polyQ) expanded proteins misfold and aggregate within the cell. Preventing aggregation of polyQ proteins through molecular or pharmacological approaches provide therapeutic advantage in animal models of HD and SCA3. I hypothesized that the UL97 kinase encoded by the human cytomegalovirus (HCMV) may be able to prevent the aggregation of polyQ proteins. Initially, I showed that the UL97 kinase prevents the deposition of aggregates of two non-polyQ proteins: the Golgi protein GCP-170 (GFP170*); and the nuclear Werner Syndrome protein (WRN). Subsequently, I uncovered that UL97 prevents the deposition of aggregates of both polyQ huntingtin and ataxin 3. UL97 dispersed nuclear PML bodies and decreased p53-mediated transcription. These results identify UL97 as a novel tool to probe the cellular mechanisms that contribute to the formation of aggregates in polyQ disorders. Project 2: A major challenge in the field is to understand the mechanisms involved in the trafficking of transmembrane proteins to cilia. I hypothesized that a network of proteins functions within the secretory and the endosomal pathways to regulate the delivery of signaling proteins to cilia. To identify pathways and components of cellular machinery involved in ciliary trafficking, I tracked the transport of a ciliary cargo somatostain receptor 3 (SSTR3). I showed that SSTR3 localizes to cilia of inner medullary collecting duct cells (IMCDs). SSTR3 is also found in the early and recycling endosomes identified by labeling with the endosomal markers Rab5, Rab21, Rab4, and Rab11. Using time-lapse imaging, I observed the delivery of SSTR3 from endosomal compartments to the base of cilia. SSTR3 segregates within Rab21- and Rab4-containing subdomains of early endosomes and expression of dominant inactive mutants of Rab21, Rab4, and Rab11 severely impairs SSTR3 trafficking. My findings defined a novel role for Rab21 and Rab4 in ciliary trafficking. My work will pave the way towards better understanding of the mechanisms that regulate cilia traffic.

1 online resource (xiv, 132 p. : ill., digital, PDF file)

Cell Biology;

Joint Health Sciences;

UL97 kinase polyQ aggregation huntington's disease SSTR3 Rab21 cilia

UNRESTRICTED

Advisors/Committee Members: Sztul, Elizabeth S., Collawn, James<br>, Kirk, Kevin<br>, Theibert, Anne Burton<br>, Yoder, Bradley K..

Subjects/Keywords: Cilia<; br>; Cytomegalovirus  – enzymology<; br>; Huntington Disease  – virology<; br>; Neurons  – metabolism<; br>; Peptides  – antagonists & inhibitors<; br>; Phosphotransferases (Alcohol Group Acceptor)  – physiology<; br>; Spinocerebellar Ataxias  – virology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Tower-Gilchrist, C. (. D. (2011). The role of protein folding and protein trafficking in human disease. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,964

Chicago Manual of Style (16th Edition):

Tower-Gilchrist, Cristy (Cristy Davette). “The role of protein folding and protein trafficking in human disease.” 2011. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 16, 2019. http://contentdm.mhsl.uab.edu/u?/etd,964.

MLA Handbook (7th Edition):

Tower-Gilchrist, Cristy (Cristy Davette). “The role of protein folding and protein trafficking in human disease.” 2011. Web. 16 Nov 2019.

Vancouver:

Tower-Gilchrist C(D. The role of protein folding and protein trafficking in human disease. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2011. [cited 2019 Nov 16]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,964.

Council of Science Editors:

Tower-Gilchrist C(D. The role of protein folding and protein trafficking in human disease. [Doctoral Dissertation]. University of Alabama – Birmingham; 2011. Available from: http://contentdm.mhsl.uab.edu/u?/etd,964

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