subject:(Macropinocytosis)

1. NOFAL, MICHEL. Catabolism of Extracellular Protein by Pancreatic Cancer Cells .

Degree: PhD, 2018, Princeton University

URL: http://arks.princeton.edu/ark:/88435/dsp017w62fb98p

► All cells require amino acids to support protein synthesis and cell growth. Until recently, mammalian cells were thought to depend on monomeric amino acids in… (more)

▼ All cells require amino acids to support protein synthesis and cell growth. Until recently, mammalian cells were thought to depend on monomeric amino acids in the environment. I showed that pancreatic tumor cells can use extracellular protein as a source of amino acids. These cells take up intact protein via macropinocytosis and catabolize it in lysosomes. This process – “protein eating” – enables cultured pancreatic cancer cells to grow in amino acid-deficient environments. In this thesis, I present my work on protein eating. To show that protein eating is capable of fueling growth, I cultured murine pan- creatic cancer cells in medium lacking leucine (an essential amino acid) and supple- mented with a physiological concentration of serum albumin. Many cells cells died in this medium, but some survived and grew to confluence. I passaged these survivors for months, and they gradually adapted to growth fueled by protein eating. This proved that protein eating is a viable form of amino acid uptake. I developed isotope tracer-based methods to quantitatively measure protein eating. Cells are grown in medium with stable isotope-labeled amino acids and unlabeled serum protein. Mass spectrometry enables distinction of amino acids taken up as monomers (labeled) from amino acids taken up as intact protein and catabolized (unlabeled). I conducted genome-wide screens to systematically identify genes essential for growth fueled by protein eating. The most essential gene was GCN2, which suppresses translation initiation in cells starved for amino acids. I discovered that loss of GCN2 impairs catabolism in amino acid-deprived cells. I propose that GCN2 supports catabolism by directing amino acids emerging from lysosomes into newly synthesized proteins that increase the catabolic capacity of the cell – for example, the lysosomal hydrolase cathepsin L. Advances in our understanding of protein eating may lead to the development of better therapies for pancreatic cancer patients. The importance of protein eating as an amino acid supply route for cells in healthy tissues remains unexplored. Advisors/Committee Members: Rabinowitz, Joshua D (advisor).

Subjects/Keywords: Macropinocytosis; Pancreas cancer; Protein catabolism

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APA (6^th Edition):

NOFAL, M. (2018). Catabolism of Extracellular Protein by Pancreatic Cancer Cells . (Doctoral Dissertation). Princeton University. Retrieved from http://arks.princeton.edu/ark:/88435/dsp017w62fb98p

Chicago Manual of Style (16^th Edition):

NOFAL, MICHEL. “Catabolism of Extracellular Protein by Pancreatic Cancer Cells .” 2018. Doctoral Dissertation, Princeton University. Accessed January 17, 2021. http://arks.princeton.edu/ark:/88435/dsp017w62fb98p.

MLA Handbook (7^th Edition):

NOFAL, MICHEL. “Catabolism of Extracellular Protein by Pancreatic Cancer Cells .” 2018. Web. 17 Jan 2021.

Vancouver:

NOFAL M. Catabolism of Extracellular Protein by Pancreatic Cancer Cells . [Internet] [Doctoral dissertation]. Princeton University; 2018. [cited 2021 Jan 17]. Available from: http://arks.princeton.edu/ark:/88435/dsp017w62fb98p.

Council of Science Editors:

NOFAL M. Catabolism of Extracellular Protein by Pancreatic Cancer Cells . [Doctoral Dissertation]. Princeton University; 2018. Available from: http://arks.princeton.edu/ark:/88435/dsp017w62fb98p

Vanderbilt University

2. Kilchrist, Kameron V. Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes.

Degree: MS, Biomedical Engineering, 2016, Vanderbilt University

URL: http://hdl.handle.net/1803/11645

► Electrostatic complexation of a cationic MAPKAP kinase 2 inhibitory (MK2i) peptide with the anionic, pH-responsive polymer poly(propylacrylic acid) (PPAA) yields MK2i nano-polyplexes (MK2i-NPs) that significantly… (more)

Subjects/Keywords: macropinocytosis; pH-responsive; endosome escape; nanoparticle; Drug delivery; vascular therapeutic

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APA (6^th Edition):

Kilchrist, K. V. (2016). Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11645

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):

Kilchrist, Kameron V. “Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes.” 2016. Thesis, Vanderbilt University. Accessed January 17, 2021. http://hdl.handle.net/1803/11645.

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

MLA Handbook (7^th Edition):

Kilchrist, Kameron V. “Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes.” 2016. Web. 17 Jan 2021.

Vancouver:

Kilchrist KV. Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes. [Internet] [Thesis]. Vanderbilt University; 2016. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1803/11645.

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

Council of Science Editors:

Kilchrist KV. Mechanism of Enhanced Cellular Uptake and Cytosolic Retention of MK2 Inhibitory Peptide Nano-polyplexes. [Thesis]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/11645

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

University of Saskatchewan

3. Bodnarchuk, Timothy. Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death.

Degree: 2011, University of Saskatchewan

URL: http://hdl.handle.net/10388/etd-06222011-145925

► Medulloblastoma cells do not contain detectable amounts of the bZIP protein Zhangfei. However, previous work has shown that expression of this protein in cells of… (more)

▼ Medulloblastoma cells do not contain detectable amounts of the bZIP protein Zhangfei. However, previous work has shown that expression of this protein in cells of the ONS-76 line, derived from a human medulloblastoma, causes the cells to stop growing and develop processes that resemble neuritis (a characteristic of differentiated neurons). Zhangfei-expressing cells eventually die. My objective was to determine the molecular mechanisms by which Zhangfei influences ONS-76 cells. My strategy was to infect ONS-76 cells with adenovirus vectors expressing either Zhangfei or the control E. coli protein â-galactosidase (LacZ) and then to compare the following parameters in Zhangfei and LacZ-expressing cells: a) markers of apoptosis, autophagy and macropinocytosis (the three main pathways of cell death); b) transcripts for genes involved in neurogenesis and apoptosis; c) phosphorylation of peptide targets of selected cellular protein kinases; and d) active transcription factors. Zhangfei-expressing cells appeared to succumb to apoptosis as determined by the expression of phosphatidylserine on the cell surface and intensity of nuclear staining with the DNA dye Hoechst. Increased staining for autophagic vesicles and upregulated expression of autophagy response genes in these cells indicated that they were undergoing autophagy, possibly associated with apoptosis. My analysis of steady-state transcripts for genes involved in apoptosis and neurogenesis and functional protein kinases in Zhangfei-expressing cells indicated that the mitogen-activated protein kinase (MAPK) pathway was active in these cells. In addition, I found that the transcription factor Brn3a as well as factors implicated in differentiation were also active. These observations led me to hypothesize that Zhangfei enhances the expression of Brn3a, a known inducer of TrkA, the high-affinity receptor for nerve growth factor (NGF). TrkA then binds in an autocrine manner to NGF, triggering the MAPK pathway and leading to differentiation of ONS-76 cells into neuron and glia-like cells, eventually bringing about cell death by apoptosis and autophagy. I tested this hypothesis by showing that Zhangfei could enhance transcription from the isolated Brn3a promoter, that ONS-76 cells produce NGF as detected in a bioassay, and that antibodies against NGF and inhibitors of TrkA and selected components of the MAPK pathway could partially restore the growth of Zhangfei-expressing ONS-76 cells. My work supports previous work highlighting the importance of NGF-TrkA signaling in the outcome of medulloblastomas and shows how Zhangfei is able to trigger this pathway. Advisors/Committee Members: Misra, Vikram, Mousseau, Darrell, Napper, Scott, Bonham, Keith, Hill, Janet.

Subjects/Keywords: Zhangfei; autophagy; apoptosis; Brn3a; medulloblastoma; MapK; TrkA; macropinocytosis

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APA (6^th Edition):

Bodnarchuk, T. (2011). Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/etd-06222011-145925

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):

Bodnarchuk, Timothy. “Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death.” 2011. Thesis, University of Saskatchewan. Accessed January 17, 2021. http://hdl.handle.net/10388/etd-06222011-145925.

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

MLA Handbook (7^th Edition):

Bodnarchuk, Timothy. “Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death.” 2011. Web. 17 Jan 2021.

Vancouver:

Bodnarchuk T. Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death. [Internet] [Thesis]. University of Saskatchewan; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10388/etd-06222011-145925.

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

Council of Science Editors:

Bodnarchuk T. Zhangfei suppresses the growth of Medulloblastoma cells and commits them to programmed cell death. [Thesis]. University of Saskatchewan; 2011. Available from: http://hdl.handle.net/10388/etd-06222011-145925

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

University of Toronto

4. Ostrowski, Philip. Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting.

Degree: PhD, 2020, University of Toronto

URL: http://hdl.handle.net/1807/101146

► Professional phagocytes actively patrol the tissues to remove debris, pathogens, and apoptotic bodies. This daunting task requires clearance of hundreds of billions of apoptotic cells… (more)

Subjects/Keywords: Cresyl violet; Lysosome; Macrophage; Macropinocytosis; Phagocytosis; Podosome; 0379

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

APA (6^th Edition):

Ostrowski, P. (2020). Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/101146

Chicago Manual of Style (16^th Edition):

Ostrowski, Philip. “Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting.” 2020. Doctoral Dissertation, University of Toronto. Accessed January 17, 2021. http://hdl.handle.net/1807/101146.

MLA Handbook (7^th Edition):

Ostrowski, Philip. “Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting.” 2020. Web. 17 Jan 2021.

Vancouver:

Ostrowski P. Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting. [Internet] [Doctoral dissertation]. University of Toronto; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1807/101146.

Council of Science Editors:

Ostrowski P. Macrophage Surveillance and Immunity: Eating, Drinking, and Digesting. [Doctoral Dissertation]. University of Toronto; 2020. Available from: http://hdl.handle.net/1807/101146

5. Fletcher, Katherine Anne. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.

Degree: PhD, 2019, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/291925

► Autophagy is a well-studied catabolic process through which cytoplasmic components are targeted for lysosomal degradation by autophagosomes. A key step in this process is the… (more)

▼ Autophagy is a well-studied catabolic process through which cytoplasmic components are targeted for lysosomal degradation by autophagosomes. A key step in this process is the recruitment, processing and lipidation of LC3 to autophagosomes. Recently it has become increasingly apparent that, through the unconventional use of some autophagy related proteins, LC3 can also become lipidated to distinct non-autophagosomal membranes of the endolysosomal system. This process is termed non-canonical autophagy and occurs independently of conventional autophagy initiation signals. Non-canonical autophagy usually occurs after macro endocytic engulfment events such as macropinocytosis, entosis and LC3 associated phagocytosis (LAP). Certain ionophores and lysosomotropic drugs, such as monensin, can also activate this process and promote LC3 lipidation to lysosomes. This project focuses on Atg16L1, an essential autophagy protein that directs the membrane site where LC3 is lipidated. Atg16L1 is relatively well characterised in autophagy but little is known about the mechanisms underlying its role in non-canonical autophagy. This project used a structure/function approach to assess the importance of different domains of Atg16L1 in the context of autophagy versus non-canonical autophagy. I have demonstrated for the first time, that the Atg16L1 C-terminal WD40 domain (CTD) is dispensable for its role in autophagy but essential for LC3 lipidation during non-canonical autophagy. Furthermore, single point mutants were uncovered in the CTD of Atg16L1 that likewise are dispensable for autophagy but fundamental to LC3 lipidation in non-canonical autophagy. These data provide a novel strategy for dissecting canonical and non-canonical autophagy pathways at a molecular level. This project used an existing mouse model with an Atg16L1 truncation (lacking the CTD and nearby residues) and implicated the lack of non canonical autophagy to a defect in MHCII antigen presentation. Furthermore this project has generated new refined Atg16L1 mutant models ablating non-canonical autophagy without affecting canonical autopahgy. In parallel, proteomic analysis was done to provide mechanistic insights into Atg16L1 binding partners in the context of non-canonical autophagy.

Subjects/Keywords: autophagy; non-canonical autophagy; LC3 associated phagocytosis; macropinocytosis

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APA (6^th Edition):

Fletcher, K. A. (2019). Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/291925

Chicago Manual of Style (16^th Edition):

Fletcher, Katherine Anne. “Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 17, 2021. https://www.repository.cam.ac.uk/handle/1810/291925.

MLA Handbook (7^th Edition):

Fletcher, Katherine Anne. “Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.” 2019. Web. 17 Jan 2021.

Vancouver:

Fletcher KA. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 17]. Available from: https://www.repository.cam.ac.uk/handle/1810/291925.

Council of Science Editors:

Fletcher KA. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://www.repository.cam.ac.uk/handle/1810/291925

Florida International University

6. Sharief, Mujataba Rahiman. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.

Degree: PhD, Biochemistry, 2016, Florida International University

URL: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

► Dictyostelium discoideum is a soil dwelling amoeba which has been widely used as a model organism to study cellular processes such as signal transduction,… (more)

▼ Dictyostelium discoideum is a soil dwelling amoeba which has been widely used as a model organism to study cellular processes such as signal transduction, chemotaxis, endocytosis and exocytosis. The process of phagocytosis in Dicytostelium is largely comparable to that of neutrophils and macrophages in the mammalian system. Neutrophils and macrophages are cells of the innate immune system and they engulf infectious bacteria through phagocytosis. Dictyostelium cells uptake yeast and bacteria for their nutrition through phagocytosis, which is an actin dependent mechanism and is a target of multiple signaling inputs. Recent studies have uncovered different proteins involved in the signaling of particle and further studies are required to decipher the intricate mechanism leading to the F-actin rearrangement. Two of the proteins have previously known to be involved in the pathways regulating the F- actin rearrangement name PP2A phosphatase and LKB1 kinase The main objective of this project was to determine how these proteins are affecting the two actin driven particle uptake processes, phagocytosis and fluid uptake. We showed that ablation of PsrA gene which codes the regulatory subunit of PP2A resulted in a defective phagocytosis, whereas the fluid uptake was normal. We also showed for the first time that there was an increase in the phosphorylation of some of the PKB substrate proteins in wild type cell. Cells lacking PsrA gene displayed an aberrant phosphorylation of PKB substrate protein when compared to the wild type cells further confirming the involvement of PKB substrate in phagocytosis. Further, we looked at the effects of LKB1 kinase on phagocytosis by using a LKB1 knockdown construct introduced into wild type cells. The knock down of LKB1 resulted in a higher rate of phagocytosis while introduction of a LKB1 over expressing construct severally decreased the rate of phagocytosis indicating an inhibitory effect of LKB1. Furthermore there was an increase in the PKB substrate protein but a different pattern compared to the psrA^-cells. We also carried out adhesion assays on LKB1 knockdown cells and the results showed a higher substrate adhesion as compared to the wild type cells, while psrA^-cells had no adhesion defect. Advisors/Committee Members: Dr. Lou W. Kim, Dr. Lidia Kos, Dr. Xiaotang Wang, Dr. Yukching Tse-Dinh, Dr. Mauricio Rodriguez-Lannetty.

Subjects/Keywords: PP2A/B56; LKB1; Phagocytosis; Macropinocytosis; Biochemistry; Cell Biology; Molecular Biology

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APA (6^th Edition):

Sharief, M. R. (2016). Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

Chicago Manual of Style (16^th Edition):

Sharief, Mujataba Rahiman. “Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.” 2016. Doctoral Dissertation, Florida International University. Accessed January 17, 2021. https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781.

MLA Handbook (7^th Edition):

Sharief, Mujataba Rahiman. “Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum.” 2016. Web. 17 Jan 2021.

Vancouver:

Sharief MR. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2016. [cited 2021 Jan 17]. Available from: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781.

Council of Science Editors:

Sharief MR. Regulation of Particle Uptake by PP2A/B56 and LKB1 in Dictyostelium Discoideum. [Doctoral Dissertation]. Florida International University; 2016. Available from: https://digitalcommons.fiu.edu/etd/2539 ; 10.25148/etd.FIDC000781 ; FIDC000781

7. Monga, Louise. Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes.

Degree: MS, Biology and Microbiology, 2018, South Dakota State University

URL: https://openprairie.sdstate.edu/etd/2698

► Understanding macrophage cell biology is important due to macrophages key roles in human health and diseases including proper immune function, wound healing, atherosclerosis, and… (more)

Subjects/Keywords: CSF-1R; macropinocytosis; Ptpn6; Biology; Cell and Developmental Biology

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APA (6^th Edition):

Monga, L. (2018). Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes. (Masters Thesis). South Dakota State University. Retrieved from https://openprairie.sdstate.edu/etd/2698

Chicago Manual of Style (16^th Edition):

Monga, Louise. “Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes.” 2018. Masters Thesis, South Dakota State University. Accessed January 17, 2021. https://openprairie.sdstate.edu/etd/2698.

MLA Handbook (7^th Edition):

Monga, Louise. “Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes.” 2018. Web. 17 Jan 2021.

Vancouver:

Monga L. Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes. [Internet] [Masters thesis]. South Dakota State University; 2018. [cited 2021 Jan 17]. Available from: https://openprairie.sdstate.edu/etd/2698.

Council of Science Editors:

Monga L. Identification of Macropinocytosis Regulating proteins and Signaling from Macropinosomes. [Masters Thesis]. South Dakota State University; 2018. Available from: https://openprairie.sdstate.edu/etd/2698

University of California – Irvine

8. Kim, Seong Min. Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds.

Degree: Biological Sciences, 2016, University of California – Irvine

URL: http://www.escholarship.org/uc/item/9wr99118

► Despite the advances in therapeutics targeting key players that drive cancer metabolism, clinical benefits of these therapies have been limited. As tumors consist of heterogeneous… (more)

▼ Despite the advances in therapeutics targeting key players that drive cancer metabolism, clinical benefits of these therapies have been limited. As tumors consist of heterogeneous population of cells, targeting a specific oncoprotein may provide selective advantage to cancer cells that are not driven by that oncoprotein. Also, upregulation of anabolic pathways that are not being directly targeted may also contribute to development of resistance to the therapy. Instead of focusing on a specific metabolic protein, our lab is interested in striking cancer metabolism at its apex—cancer cells’ dependence on nutrients. To fuel constitutive anabolism and proliferation, cancer cells must have influx of nutrients. When nutrients become limiting, unlike non-transformed cell that can discontinue anabolic processes and become quiescent, cancer cells undergo metabolic chaos as oncogene-driven growth signals continue to force anabolism. Developing a therapy against this cancer-specific phenotype will have efficacy against broad classes of cancers as all cancers need nutrients to survive. In searching for a compound that can inhibit nutrient uptake, our lab has been focusing on sphingolipids, a class of bioactive lipid that plays important roles in cellular functions including membrane biology. In yeast, stress-induced nutrient transporter down-regulation is regulated by sphingolipid phytosphingosine. Sphingolipid ceramide down-regulates nutrient transporters in mammalian cells. A sphingolipid-derived compound FTY720 is also able to trigger surface amino acid and glucose transporter loss. FTY720, an FDA-approved drug for treatment of multiple sclerosis, has anti-cancer activities in a various cancer models. Unfortunately, FTY720 causes bradycardia at the doses needed for anti-neoplastic effects. However, mechanism by which FTY720 kills cancer cells is completely separate from its effect on heart rate. SH-BC-893 is a constrained analog of FTY720 that lacks its dose-limiting side effect but retains anti-neoplastic activities. SH-BC-893, like ceramide and FTY720, down-regulates surface nutrient transporters. In addition, SH-BC-893 induces cytoplasmic vacuolation secondary to mis-localization of lipid kinase PIKfyve. This blocks lysosomal degradation of autophagosomes and macropinosomes, alternate nutrient acquisition pathways cancer cells can use to adapt to nutrient stress triggered by loss of surface nutrient transporters. LDL receptors are also down-regulated and LDL degradation is blocked by SH-BC-893. Prostate cancers rely heavily on LDL uptake for growth and proliferation and are thereby very sensitive to SH-BC-893. Surprisingly, prostate cancer cells are resistant to amino acid and glucose withdrawal. Our ongoing works have uncovered that this is because PTEN loss in prostate cancers upregulates macropinocytosis. This previously-unappreciated macropinocytosis in prostate cancers requires AMPK activation. Our works demonstrate that prostate cancer cells can use macropinocytosis to consume necrotic debris…

Subjects/Keywords: Biology; Cellular biology; Autophagy; Cancer biology; Cancer metabolism; Cancer therapy; Macropinocytosis; Nutrient transporters

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APA (6^th Edition):

Kim, S. M. (2016). Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/9wr99118

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):

Kim, Seong Min. “Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds.” 2016. Thesis, University of California – Irvine. Accessed January 17, 2021. http://www.escholarship.org/uc/item/9wr99118.

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

MLA Handbook (7^th Edition):

Kim, Seong Min. “Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds.” 2016. Web. 17 Jan 2021.

Vancouver:

Kim SM. Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds. [Internet] [Thesis]. University of California – Irvine; 2016. [cited 2021 Jan 17]. Available from: http://www.escholarship.org/uc/item/9wr99118.

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

Council of Science Editors:

Kim SM. Simultaneously inhibiting multiple nutrient acquisition pathways using synthetic sphingolipid compounds. [Thesis]. University of California – Irvine; 2016. Available from: http://www.escholarship.org/uc/item/9wr99118

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

University of Michigan

9. Wong, Amanda. Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages.

Degree: PhD, Immunology PhD, 2020, University of Michigan

URL: http://hdl.handle.net/2027.42/155197

► As professional phagocytes, macrophages are susceptible to endolysosomal membrane damage inflicted by the pathogens and noxious particles they ingest. Whether macrophages have mechanisms for limiting… (more)

▼ As professional phagocytes, macrophages are susceptible to endolysosomal membrane damage inflicted by the pathogens and noxious particles they ingest. Whether macrophages have mechanisms for limiting such damage is a fundamental question of macrophage biology that is poorly understood. Previously we reported a phenomenon, termed “inducible renitence,” in which LPS activation of macrophages protected their endolysosomes from membrane damage initiated by the phagocytosis of silica beads. In this thesis, I uncover mechanistic details of the underlying process and more broadly define the immune contexts in which renitence can be induced. Applying a quantitative, fluorescence microscopy assay for measuring lysosomal damage, I determined that mechanistically renitence limits the release of small but not large molecules from lysosomes by restricting the time window of release. Morphological analysis of a large imaging data set derived from these studies led to the discovery of a novel, structural correlate of renitence: large, damage-resistant vacuoles that form adjacent to bead-containing phagosomes in LPS-activated but not resting macrophages. These structures, which we term “renitence vacuoles” (RVs), formed coincident with silica bead uptake in a process associated with macropinocytosis, and persisted around bead-containing phagosomes. RVs fused with lysosomes, whereas phagosomes associated with RVs did not, consistent with a model in which RVs act as structural barriers to prevent fusion between damaged phagosomes and intact lysosomes. Complementing these studies of cellular mechanism, several molecular candidates – namely, cholesterol, synaptotagmin-7, and the autophagy component Atg7 - were evaluated for their contribution to renitence based on their established roles in resistance against or repair of organellar damage in other contexts. However, none of these factors were found to definitively underlie renitence. A growing body of literature finds evidence for the existence of several functionally distinct macrophage populations in vivo. To expand our understanding of the inflammatory contexts in which renitence acts, I examined whether macrophages of these well-defined subtypes exhibit renitence. These studies revealed that classically activated and regulatory macrophages, but not alternatively activated macrophages, exhibit renitence. Furthermore, stimulation of a subset of Toll-like receptors was sufficient to induce renitence. Of the macrophage subtypes examined, those harboring the greatest capacity for renitence shared similarities in their cytokine secretion profile. Likewise, macrophages subtypes less capable of inducing renitence possessed a common profile of cytokine secretion distinct from that associated with renitent macrophages. Thus, the polarization state of macrophages influences their susceptibility to lysosomal damage. Taken together, this work establishes renitence as an activity of macrophages specialized in host defense or immune regulation and identifies a novel mechanism… Advisors/Committee Members: Swanson, Joel A (committee member), Swanson, Michele S (committee member), Lieberman, Andrew P (committee member), Moore, Bethany B (committee member), O'Riordan, Mary X D (committee member).

Subjects/Keywords: Macrophages; LPS; Lysosomal damage; Inducible renitence; Macropinocytosis; Macrophage activation; Microbiology and Immunology; Health Sciences; Science

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APA (6^th Edition):

Wong, A. (2020). Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/155197

Chicago Manual of Style (16^th Edition):

Wong, Amanda. “Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages.” 2020. Doctoral Dissertation, University of Michigan. Accessed January 17, 2021. http://hdl.handle.net/2027.42/155197.

MLA Handbook (7^th Edition):

Wong, Amanda. “Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages.” 2020. Web. 17 Jan 2021.

Vancouver:

Wong A. Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages. [Internet] [Doctoral dissertation]. University of Michigan; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2027.42/155197.

Council of Science Editors:

Wong A. Cellular Mechanisms and Immunological Contexts of Lysosomal Damage Protection in Macrophages. [Doctoral Dissertation]. University of Michigan; 2020. Available from: http://hdl.handle.net/2027.42/155197

Missouri University of Science and Technology

10. Xu, Yi. Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake.

Degree: M.S. in Applied and Environmental Biology, Applied and Environmental Biology, Missouri University of Science and Technology

URL: https://scholarsmine.mst.edu/masters_theses/4735

► "Luminescent semiconductor quantum dots (QDs) have recently been used for delivering and monitoring biomolecules, such as drugs and proteins. However, QDs alone have a very… (more)

Subjects/Keywords: Macropinocytosis; Nona-arginine; Biology; Environmental Sciences

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

APA (6^th Edition):

Xu, Y. (n.d.). Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake. (Masters Thesis). Missouri University of Science and Technology. Retrieved from https://scholarsmine.mst.edu/masters_theses/4735

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16^th Edition):

Xu, Yi. “Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake.” Masters Thesis, Missouri University of Science and Technology. Accessed January 17, 2021. https://scholarsmine.mst.edu/masters_theses/4735.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7^th Edition):

Xu, Yi. “Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake.” Web. 17 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Xu Y. Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake. [Internet] [Masters thesis]. Missouri University of Science and Technology; [cited 2021 Jan 17]. Available from: https://scholarsmine.mst.edu/masters_theses/4735.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Xu Y. Nona-arginine peptides facilitate cellular entry of semiconductor nanocrystals: mechanisms of uptake. [Masters Thesis]. Missouri University of Science and Technology; Available from: https://scholarsmine.mst.edu/masters_theses/4735

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Florida International University

11. Gu, Cong. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.

Degree: PhD, Biochemistry, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

► Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and… (more)

▼ Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and initiates the human innate immune response or serve as a direct entry route for productive infection of pathogen. Dictyostelium discoideum, soil-living amoeba, a unicellular eukaryote that could professionally internalize fluid phase or particles several folds more than that of macrophages and neutrophils. Additionally, multiple key signaling pathways are conserved between Dictyostelium and mammalian cells, including pathways affecting small GTPases Ras and Rac and their downstream effectors, and F-Actin remodeling. All these traits makes Dictyostelium an excellent model organism to study the process pf macropinocytosis and phagocytosis. Upon internalization of the prey, these macropinocytes and phagocytes are often in an environment of increased production of superoxide radicals in the prey-containing vesicles, which helps stimulates the downstream signaling pathways to digest the prey inside. However, the mechanism of how superoxide regulates the process of macropinocytosis and phagocytosis is not fully understood. We had previously reported that Dictyostelium cells lacking Superoxide dismutase C (SodC) exhibited aberrantly high level of active RasG, high basal level of Phosphatidylinositol-3,4,5-triphosphate (PIP3), and severe chemotaxis defects. Now we report that sodC^- cells displayed aberrant endosomal vesicle trafficking, significantly compromised particle uptake and defective cell to substratum matrix adhesion compared to that of wild type cells. By using high resolution live imaging microscope we also show that sodC^- cells have defects in F-Actin remodeling at the phagocytic rim extension and F-Actin depolymerization of the nascent phagosome. Interestingly, the introduction of overexpressing of cytoplasmic superoxide dismutase (SodA), redox insensitive RasG (C118A) or treatment of PI3K inhibitor LY294002 in sodC^- cells significantly rescued the defects of endosomal vesicle trafficking, particle uptake and adhesion. This project suggests that superoxide dismutase C regulates the endosomal vesicle trafficking, phagocytosis and cell to substratum matrix adhesion through the RasG/PI3K signaling axis in Dictyostelium cells. Advisors/Committee Members: Lou Kim, Xiaotang Wang, Lidia Kos, Jessica Liberles.

Subjects/Keywords: Superoxide Dismutase C; Macropinocytosis; Phagocytosis; Dictyostelium Discoideum; Biochemistry; Cell Biology; Molecular Biology

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APA (6^th Edition):

Gu, C. (2018). Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

Chicago Manual of Style (16^th Edition):

Gu, Cong. “Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.” 2018. Doctoral Dissertation, Florida International University. Accessed January 17, 2021. https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020.

MLA Handbook (7^th Edition):

Gu, Cong. “Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum.” 2018. Web. 17 Jan 2021.

Vancouver:

Gu C. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2021 Jan 17]. Available from: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020.

Council of Science Editors:

Gu C. Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum. [Doctoral Dissertation]. Florida International University; 2018. Available from: https://digitalcommons.fiu.edu/etd/3887 ; FIDC007020

Vanderbilt University

12. Freeman, Megan Culler. Cell Biology of Coronavirus Replication.

Degree: PhD, Microbiology and Immunology, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/13777

► Coronaviruses (CoVs) are positive-strand RNA viruses that induce modifications to host-cell cytoplasmic membranes during formation of replication complexes. While important for viral replication, the dynamics… (more)

▼ Coronaviruses (CoVs) are positive-strand RNA viruses that induce modifications to host-cell cytoplasmic membranes during formation of replication complexes. While important for viral replication, the dynamics of this process remain poorly understood. Existing reagents largely limited the study of these processes to fixed times, so I developed reporter viruses containing green fluorescent protein or firefly luciferase as a fusion with nonstructural protein (nsp) 2 or 3 to quantitate replication complex formation and virus replication in real time. These viruses replicated with kinetics similar to WT, demonstrating that the CoV genome has the flexibility to accommodate foreign gene addition, despite being the largest replicating RNA molecule. Use of these viruses in live-cell imaging experiments revealed continuous plasma membrane ruffling, vesicle internalization, and production of extended filopodia during CoV infection. Using several complementary techniques, I demonstrate that these membrane rearrangements are due to continuous macropinocytosis induced late during SARS-CoV and MHV infection. Additionally, I discovered that the presence of fusogenic spike on the cell surface was required for macropinocytosis induction, and that this was dependent upon EGFR activation. Ultimately, these results are the first to demonstrate the use of macropinocytosis independent from virus entry, and suggest that CoVs could exploit macropinocytosis to facilitate cell-to-cell spread during infection. During this work, a new CoV, Middle East Respiratory Syndrome (MERS) CoV, emerged in Saudi Arabia. Due to our interest in replication complex formation and membrane rearrangements, we developed a panel of antibodies to recognize MERS-CoV nsps. Several of these antibodies were highly specific for MERS-CoV nsps, allowing us to investigate the spatial and temporal formation of replication complexes in relation to cellular markers. This work is the first to visualize formation of these complexes during MERS-CoV infection and provides new reagents critical for future studies. Overall, my work has used novel reporter viruses to demonstrate the flexibility of the CoV genome, quantitate replication complex formation during infection, and provide early measurement of viral translation. Furthermore, I identified a novel function for viral exploitation of macropinocytosis and defined new virus-host interactions required for efficient CoV replication through the potential interaction of spike and EGFR. Advisors/Committee Members: Mark Denison (committee member), Jim Goldenring (committee member), Alissa Weaver (committee member), Earl Ruley (committee member), John Williams (Committee Chair).

Subjects/Keywords: cell to cell spread; macropinocytosis; fluorescent reporter viruses; MHV; MERS-CoV; SARS-CoV; Coronaviruses; virology; viral replication

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

APA (6^th Edition):

Freeman, M. C. (2014). Cell Biology of Coronavirus Replication. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13777

Chicago Manual of Style (16^th Edition):

Freeman, Megan Culler. “Cell Biology of Coronavirus Replication.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 17, 2021. http://hdl.handle.net/1803/13777.

MLA Handbook (7^th Edition):

Freeman, Megan Culler. “Cell Biology of Coronavirus Replication.” 2014. Web. 17 Jan 2021.

Vancouver:

Freeman MC. Cell Biology of Coronavirus Replication. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1803/13777.

Council of Science Editors:

Freeman MC. Cell Biology of Coronavirus Replication. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/13777

Freie Universität Berlin

13. John, Lena. Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies.

Degree: 2014, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-12366

► A main feature of the inflammatory bowel disease Crohn’s disease is the increased permeability of the disturbed intestinal barrier. In this study we investigated several… (more)

▼ A main feature of the inflammatory bowel disease Crohn’s disease is the increased permeability of the disturbed intestinal barrier. In this study we investigated several mediators pertinent to Crohn’s disease in regard to their ability to enhance transcytosis. In particular we investigated the effects of IL-1β, IL-4, IL-6, TNFα, IFNγ and histamine on the human colon carcinoma cell line T84, which was chosen because of its endocytotic properties. As a marker for transcytosis we used horseradish peroxidase (HRP). Only IL-4 increased the permeability for HRP to a relevant extent. Therefore, the impact of this cytokine on other barrier properties was investigated. The influence of IL-4 on the expression of the tight junction (TJ) proteins claudin-1, -2, -3, -4, -5, -7 and -8 as well as occludin and tricellulin was investigated by means of western blot analyses. This is the first analysis of the effect of IL-4 on TJ proteins in intestinal cells to such an extent. The channel-building claudin-2 showed an enhanced expression, whereas the expression of the tightening claudin-4 was decreased. The remaining TJ proteins remained unchanged. In addition the transepithelial resistance was analysed, which is reduced in T84 monolayers after the incubation with IL-4. By means of two-path-impedance spectroscopy we could show that the paracellular as well as the transcellular resistance were decreased by IL-4 and both account for the decrease in transepithelial resistance. The main goal of this study was to elucidate the endocytotic pathway of HRP and furthermore to study if there are additional or other pathways that are involved under inflammatory conditions, which are elicited by IL-4. For that purpose we used inhibitors specific for either clathrin mediated endocytosis, caveolin mediated endocytosis or macropinocytosis and measured the changes in the permeability for HRP in response to these inhibitors. To validate these results we established a method to immunofluorescently stain intracellular HRP. Through co-staining of several intracellular vesicles the localization of HRP in early and late stages (2 – 30 minutes) of transcytosis could be demonstrated. By means of the immunofluorescent staining and the permeability measurements we showed that HRP is transported mainly via caveolin mediated endocytosis but also via macropinocytosis. The relevance of these results for patients with Crohn’s disease was examined by comparing the permeability for HRP in patients with Crohn’s disease and healthy controls. Biopsies from both groups were treated with some of the inhibitors found to be effective in cell culture. We confirmed that the permeability for HRP of patients with Crohn’s disease is elevated compared to healthy controls and further we could show that in the native intestine the transcytosis of HRP also proceeds via caveolin mediated endocytosis and macropinocytosis. Advisors/Committee Members: w (gender), Prof. Dr. Jörg-Dieter Schulzke (firstReferee), Prof. Dr. Udo Heinemann (furtherReferee).

Subjects/Keywords: endocytosis; intestine; Crohn's disease; IL-4; clathrin; caveolin; macropinocytosis; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie

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APA (6^th Edition):

John, L. (2014). Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-12366

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):

John, Lena. “Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies.” 2014. Thesis, Freie Universität Berlin. Accessed January 17, 2021. http://dx.doi.org/10.17169/refubium-12366.

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

MLA Handbook (7^th Edition):

John, Lena. “Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies.” 2014. Web. 17 Jan 2021.

Vancouver:

John L. Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies. [Internet] [Thesis]. Freie Universität Berlin; 2014. [cited 2021 Jan 17]. Available from: http://dx.doi.org/10.17169/refubium-12366.

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

Council of Science Editors:

John L. Mechanisms of macromolecular transcytosis during Crohn's disease: investigations on the cell model T84 and human colon biopsies. [Thesis]. Freie Universität Berlin; 2014. Available from: http://dx.doi.org/10.17169/refubium-12366

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

Freie Universität Berlin

14. Japtok, Lukasz. Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells.

Degree: 2012, Freie Universität Berlin

URL: https://refubium.fu-berlin.de/handle/fub188/13092

► The lipid mediator sphingosine 1-phosphate (S1P) has been identified as a new biological molecule that is involved in the modulation of multilateral immunological processes. In… (more)

▼ The lipid mediator sphingosine 1-phosphate (S1P) has been identified as a new biological molecule that is involved in the modulation of multilateral immunological processes. In this context, topically administrated S1P inhibits the inflammatory reaction in an animal model of atopic dermatitis. Furthermore, for the first time the present work supplies clear evidence that a modulation of dendritic cell (DC) function contributes to the observed anti- inflammatory effect of local S1P application. The presence of S1P influences the essential step of DC activation, which is characterized by endocytosis of antigens. Stimulation of immature DC`s with S1P demonstrates a dose dependant reduction of antigen capture by these antigen presenting cells. In the present work, it was of great interest to specify the molecular mechanisms that lead to the S1P-induced reduction of endocytosis in immature skin DC`s. In an immature stage, DC`s are able to take up antigens via several different mechanisms. An examination of a mechanism affected by S1P indicated that this sphingolipid inhibits the screening of large volumes of fluid for antigens during macropinocytosis in DC`s. The present study shows that macropinocytosis is mediated by modulation of the PI3K activity, allowing a fine-tuned regulation of antigen capture. Furthermore, the present work indicates that S1P is able to reduce PI3K activity via the S1P2 receptor subtype. Most interestingly, down regulation of S1P2 receptor subtype not only prevents the inhibitory effect of S1P on antigen uptake but also increases the basal level of macropinocytotic capacity. These results provide evidence that S1P could be involved in the endogenous regulation of endocytosis in immature DC`s. This hypothesis has been substantiated by enhancing the endogenous biosynthesis of S1P using a direct inducer of SphK1 activity. As expected, observed reduction of endocytosis by DC`s in the presence of the SphK1 activator was accompanied by diminished phosphoinositid 3-kinase activity. In agreement with previous studies the present work provides evidence, that an ABCC1 transporter is involved in the secretion of the sphingolipid. In summary, the present work demonstrates an essential role of S1P in antigen capture by immature DC`s. Endocytosis is the initial step of the adaptive immune response. Thus, elucidation of related signalling pathways could significantly contribute to the establishment of new treatments for inflammatory diseases such as atopic dermatitis. Advisors/Committee Members: m (gender), Herr Prof. Dr. Burkhard Kleuser (firstReferee), Herr Prof. Dr. Matthias F. Melzig (furtherReferee).

Subjects/Keywords: Langerhans cells; dendritic cells; antigen; macropinocytosis; sphingosine-1-phosphate; 500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie

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

APA (6^th Edition):

Japtok, L. (2012). Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells. (Thesis). Freie Universität Berlin. Retrieved from https://refubium.fu-berlin.de/handle/fub188/13092

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):

Japtok, Lukasz. “Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells.” 2012. Thesis, Freie Universität Berlin. Accessed January 17, 2021. https://refubium.fu-berlin.de/handle/fub188/13092.

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

MLA Handbook (7^th Edition):

Japtok, Lukasz. “Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells.” 2012. Web. 17 Jan 2021.

Vancouver:

Japtok L. Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells. [Internet] [Thesis]. Freie Universität Berlin; 2012. [cited 2021 Jan 17]. Available from: https://refubium.fu-berlin.de/handle/fub188/13092.

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

Council of Science Editors:

Japtok L. Signaling of Sphingosine-1-Phosphate and its influence on endocytotic capacity of dendritic cells. [Thesis]. Freie Universität Berlin; 2012. Available from: https://refubium.fu-berlin.de/handle/fub188/13092

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

University of Western Ontario

15. Chiu, Justin K, . The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production.

Degree: 2015, University of Western Ontario

URL: https://ir.lib.uwo.ca/etd/3420

► Alzheimer’s Disease (AD) is characterized by Beta-Amyloid (Aβ) plaques within the brain. Aβ peptides are produced by the cleavage of Amyloid Precursor Protein (APP). Our… (more)

Subjects/Keywords: Alzheimer’s Disease; APP; Aβ40; Aβ42; Arf6; Rac1; Cdc42; RhoA; macropinocytosis; lysosomes; intracellular trafficking; confocal microscopy; Nervous System Diseases

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APA (6^th Edition):

Chiu, Justin K, .. (2015). The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production. (Thesis). University of Western Ontario. Retrieved from https://ir.lib.uwo.ca/etd/3420

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

Chicago Manual of Style (16^th Edition):

Chiu, Justin K, .. “The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production.” 2015. Thesis, University of Western Ontario. Accessed January 17, 2021. https://ir.lib.uwo.ca/etd/3420.

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

MLA Handbook (7^th Edition):

Chiu, Justin K, .. “The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production.” 2015. Web. 17 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

Vancouver:

Chiu, Justin K, .. The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production. [Internet] [Thesis]. University of Western Ontario; 2015. [cited 2021 Jan 17]. Available from: https://ir.lib.uwo.ca/etd/3420.

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

Council of Science Editors:

Chiu, Justin K, .. The Rho GTPases Rac1, Cdc42, and RhoA Regulate APP Transport to Lysosomes and Aβ Production. [Thesis]. University of Western Ontario; 2015. Available from: https://ir.lib.uwo.ca/etd/3420

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

University of Pennsylvania

16. Moser, Theresa S. The Role of AMPK in Viral Infection.

Degree: 2011, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/975

► Host factors are crucial in determining the outcome of viral infection. As obligate intracellular pathogens, viruses are highly dependent on numerous cellular proteins and processes,… (more)

▼ Host factors are crucial in determining the outcome of viral infection. As obligate intracellular pathogens, viruses are highly dependent on numerous cellular proteins and processes, and also must evade multiple antiviral defense mechanisms. Since viral pathogens represent a significant threat both to human health and agriculture, a better understanding of these interactions could facilitate the treatment of viral infections and provide novel targets for therapeutics. In particular, Poxviruses include medically important human pathogens yet little is known about the specific cellular factors essential for their replication. To identify genes essential for vaccinia infection, I used high-throughput RNA interference to screen Drosophila kinases and phosphatases. I identified seven genes including the three subunits of AMPK as promoting vaccinia infection. AMPK facilitated infection both in insect and mammalian cells. I found that AMPK is required for macropinocytosis, a major endocytic entry pathway for vaccinia. Furthermore, AMPK contributes to other actin-dependent cellular processes including lamellipodia formation and wound healing, independent of the known AMPK activators LKB1 and CaMKK. Therefore, AMPK plays a highly conserved role in poxvirus infection and actin dynamics independent of its role as an energy regulator. This led me to investigate the role of AMPK in other viral infections, including human arthropod-borne viral pathogens. Surprisingly I found that AMPK expression and activation restricts infection of the Bunyavirus Rift Valley Fever Virus (RVFV) in an LKB1-dependent manner. RVFV like other RNA viruses manipulates cellular membranes to form vesicle-like structures that support the viral replication complex in a process dependent on de novo fatty acid synthesis. I found that AMPK activation potently inhibits acetyl Co A carboxylase, crucial in fatty acid synthesis, leading to decreased levels of cellular lipids. Bypassing fatty acid synthesis by treating cells with palmitate, the first product of fatty acid synthesis rescued infection, demonstrating that AMPK restricts RVFV by inhibiting fatty acid synthesis. Additional RNA viruses that require membrane proliferations including the Togavirus Sindbis and the Alphavirus Vesicular Stomatitis Virus were also restricted by AMPK. AMPK is likely a component of the intrinsic innate immune response against RNA viruses, and may provide a target for broadly anti-viral therapeutics.

Subjects/Keywords: poxvirus entry; macropinocytosis; AMPK; kinase signaling; Rift Valley Fever Virus; fatty acid metabolism; Cell Biology; Virology

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APA (6^th Edition):

Moser, T. S. (2011). The Role of AMPK in Viral Infection. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/975

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):

Moser, Theresa S. “The Role of AMPK in Viral Infection.” 2011. Thesis, University of Pennsylvania. Accessed January 17, 2021. https://repository.upenn.edu/edissertations/975.

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

MLA Handbook (7^th Edition):

Moser, Theresa S. “The Role of AMPK in Viral Infection.” 2011. Web. 17 Jan 2021.

Vancouver:

Moser TS. The Role of AMPK in Viral Infection. [Internet] [Thesis]. University of Pennsylvania; 2011. [cited 2021 Jan 17]. Available from: https://repository.upenn.edu/edissertations/975.

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

Council of Science Editors:

Moser TS. The Role of AMPK in Viral Infection. [Thesis]. University of Pennsylvania; 2011. Available from: https://repository.upenn.edu/edissertations/975

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

Ohio University

17. Wang, Xuan. Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance.

Degree: PhD, Biological Sciences (Arts and Sciences), 2017, Ohio University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1505834714683835

► Cancer is the second leading cause of death in the US. Despite the endeavors and achievements made in treating cancers during the past decades, resistance… (more)

▼ Cancer is the second leading cause of death in the US. Despite the endeavors and achievements made in treating cancers during the past decades, resistance to classical chemotherapeutic agents and/or novel targeted drugs has been remaining to be a major problem in cancer therapies. Drug resistance, either existing before treatment (intrinsic) or generated after therapy (acquired), is responsible for most relapses of cancer, one of the major causes of death of the disease. Heterogeneity among patients and tumors, and the versatility of cancer to circumvent therapies make drug resistance more challenging to deal with. Better understanding the mechanisms of drug resistance is required to provide guidance to future cancer treatment and achieve better outcomes. Dysfunctional energetics and opportunistic uptake of extracellular molecules have been named as emerging hallmarks of cancer and cancer metabolism, respectively. Cancer cells are able to uptake extracellular ATP (eATP) via macropinocytosis to elevate intracellular ATP (iATP) levels, enhancing their survival in drug treatment. However, the involved drug resistance mechanisms are unknown. Here we investigated the roles of eATP as either an energy-providing or a phosphorylating molecule in general drug resistance mediated by ATP internalization and iATP elevation. We report that eATP increased iATP levels and promoted drug resistance to various tyrosine kinase inhibitors (TKIs) and chemo-drugs in human cancer cell lines of five cancer types. In A549 lung cancer cells, the resistance was downregulated by macropinocytosis inhibition or siRNA knockdown of PAK1, an essential macropinocytosis enzyme. The elevated iATP upregulated the efflux activity of ABC transporters as well as phosphorylation of PDGFRa and proteins in the PDGFR-mediated Akt-mTOR and Raf-MEK signaling pathways. Similar phosphorylation upregulations were found in A549 tumors. Meanwhile, the resistance cannot be attributed to the overall purinergic receptor-mediated signaling or intracellular ATP synthesis. These results demonstrate that eATP induces different types of drug resistance by eATP internalization and iATP elevation, implicating the ATP-rich tumor microenvironment in cancer drug resistance, expanding our understanding of the roles of eATP in the Warburg effect and offering new anticancer drug resistance targets. Advisors/Committee Members: Chen, Xiaozhuo (Advisor).

Subjects/Keywords: Biology; Cellular Biology; Molecular Biology; Cancer; drug resistance; ATP; macropinocytosis; ABC transporter; tumor microenvironment, Warburg effect

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APA (6^th Edition):

Wang, X. (2017). Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance. (Doctoral Dissertation). Ohio University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1505834714683835

Chicago Manual of Style (16^th Edition):

Wang, Xuan. “Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance.” 2017. Doctoral Dissertation, Ohio University. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1505834714683835.

MLA Handbook (7^th Edition):

Wang, Xuan. “Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance.” 2017. Web. 17 Jan 2021.

Vancouver:

Wang X. Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance. [Internet] [Doctoral dissertation]. Ohio University; 2017. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1505834714683835.

Council of Science Editors:

Wang X. Internalization of Extracellular ATP by Cancer Cells and its Functional Roles in Cancer Drug Resistance. [Doctoral Dissertation]. Ohio University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1505834714683835

Wright State University

18. Trefry, John Christopher. The Development of Silver Nanoparticles as Antiviral Agents.

Degree: PhD, Biomedical Sciences PhD, 2011, Wright State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1307721406

► Silver nanoparticles (AgNPs) have received tremendous attention for their antimicrobial properties; however, many gaps in knowledge exist. To address these issues, three research objectives… (more)

▼ Silver nanoparticles (AgNPs) have received tremendous attention for their antimicrobial properties; however, many gaps in knowledge exist. To address these issues, three research objectives were examined. The first objective hypothesized AgNPs can be size selected and concentrated via tangential flow ultrafiltration. The second objective hypothesized a high-throughput method could be developed to screen nanoparticle antiviral-activity and cytotoxicity simultaneously. The third objective hypothesized AgNPs inhibit viruses by preventing viral entry. For objective one, a tangential flow ultrafiltration scheme was tested on AgNPs synthesized via the Creighton Colloid method. AgNPs were analyzed via transmission electron microscopy. In objective two, an HIV-1 vector was adapted to 96-well format and modified to utilize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) for simultaneous cytotoxicity and antiviral measurement. The third objective was investigated using Vaccinia virus (VACV). AgNP effects on VACV entry were monitored through β-galactosidase reporter assay and confocal microscopy. Western blots detected AgNP/VACV interaction. Plaque assays monitored AgNP inhibition over the entire VACV replication cycle. MTT and trypan blue exclusion measured AgNP cytotoxicity. In objective one, tangential flow ultrafiltration demonstrated size selection and concentration of AgNPs. Filtered AgNPs were uniform and unaggregated with average 11 nm diameters. A high-throughput, standardized assay was developed in objective two. AgNPs had antiviral-activity at non-cytotoxic concentrations (IC50 = 16 μg mL-1). In the third objective, AgNPs prevented VACV entry in both cytoprotective and virucidal capacities at non-cytotoxic concentrations (IC50 = 48 μg mL-1). In the absence of macropinocytosis, AgNPs retained virucidal-activity but not cytoprotective effects. AgNPs bound to viral entry proteins. Plaque assays demonstrated that AgNPs inhibited the entire VACV replication cycle. Cytotoxicity assays demonstrated AgNPs were non-cytotoxic at antiviral concentrations. Objective one's size selection and concentration method permits accurate investigation into nanoparticle antimicrobial activity by eliminating size and reagent incompatibility problems inherent to AgNP synthesis. In objective two, the traditional viral titering assay was replaced with a standardized assay measuring simultaneously antiviral activity and cytotoxicity, permitting faster and cheaper antiviral screening of nanoparticles. In the third objective, AgNP-mediated antiviral-activity was pinpointed to viral entry. Multiple mechanisms of entry inhibition were observed. These data suggest that AgNPs can be potent and broad-spectrum antiviral agents and therapeutics. Advisors/Committee Members: Wooley, Dawn (Advisor).

Subjects/Keywords: Nanoscience; Nanotechnology; Virology; silver; nanoparticle; vaccinia; virus; nanotechnology; antiviral; entry; broad-spectrum; virucidal; cytoprotective; macropinocytosis; HIV-1; vector; high-throughput; cytotoxicity

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

APA (6^th Edition):

Trefry, J. C. (2011). The Development of Silver Nanoparticles as Antiviral Agents. (Doctoral Dissertation). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1307721406

Chicago Manual of Style (16^th Edition):

Trefry, John Christopher. “The Development of Silver Nanoparticles as Antiviral Agents.” 2011. Doctoral Dissertation, Wright State University. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1307721406.

MLA Handbook (7^th Edition):

Trefry, John Christopher. “The Development of Silver Nanoparticles as Antiviral Agents.” 2011. Web. 17 Jan 2021.

Vancouver:

Trefry JC. The Development of Silver Nanoparticles as Antiviral Agents. [Internet] [Doctoral dissertation]. Wright State University; 2011. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1307721406.

Council of Science Editors:

Trefry JC. The Development of Silver Nanoparticles as Antiviral Agents. [Doctoral Dissertation]. Wright State University; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1307721406

19. Zoller, Erin. Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis.

Degree: PhD, Medicine: Immunology, 2011, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312483784

► Anemia is a widespread and potentially serious clinical problem. Anemia caused by inflammation has been recognized for over 100 years, however the mechanisms behind anemia… (more)

▼ Anemia is a widespread and potentially serious clinical problem. Anemia caused by inflammation has been recognized for over 100 years, however the mechanisms behind anemia during acute inflammation are poorly understood. For clues as to how acute anemia during inflammation might develop, we looked to a disease called hemophagocytic lymphohistiocytosis (HLH). HLH a disorder characterized by severe, acute anemia and cytopenias in the context of exaggerated inflammation. These patients have activated, proliferating and infiltrating macrophages that have engulfed RBCs, a process called hemophagocytosis. Interferon-gamma (IFN-γ) is an inflammatory cytokine and activator of macrophages made in great excess in many HLH patients and correlated with disease severity and poor prognosis. IFN-γ has been shown to be a uniquely necessary cytokine for anemia development in mouse models of HLH. We hypothesized that IFN-γ is sufficient to cause acute consumptive anemia by directly activating macrophages to hemophagocytose blood components. We developed an in vivo IFN-γ infusion system using surgically placed osmotic pumps in mice, and we determined the extent of anemia by measuring blood hemoglobin concentration. We demonstrate that IFN-γ is sufficient, in a dose dependent manner, to cause severe and rapidly developing anemia in wild-type mice. We term this anemia ‘consumptive anemia of inflammation’ (CAI). In addition, we observed hemophagocytosis by macrophages in the tissues via microscopy and flow cytometry. We also studied IFN-γ infusion of Macrophages Insensitive to Interferon-Gamma (MIIG) mice, in which the only cell type that cannot respond to IFN-γ are the macrophages. Results revealed that IFN-γ must act on the macrophages to cause either hemophagocytosis or CAI. Our data strongly suggest that hemophagocytosis by macrophages is the main mechanism of IFN-γ driven CAI. We next aimed to examine the entirely unknown mechanisms behind the hemophagocytic process. We determined IFN-γ driven hemophagocytosis is a macropinocytic process, similar in appearance to another macropinocytic process called efferocytosis, or uptake of apoptotic cells. The similarities between hemophagocytosis and efferocytosis, along with our studies demonstrating that IFN-γ increases efferocytosis, led us to hypothesize that the two processes might share mechanisms. We examined hemophagaocytosis in terms of three important mechanisms of efferocytosis: 1) cell tethering, 2) “eat me” signals and 3) “don’t eat me” signals. We show that IFN-γ causes increased tethering of RBCs to macrophages. Tethering is accompanied by increased macrophage sensitivity to “eat me” signals. This data suggests that IFN-γ infusion causes macrophages to lower their threshold for “eat me” signals to induce engulfment. We also found that C57BL/6J mice are a strain “susceptible” to severe CAI after IFN-γ infusion, whereas 129/Sv mice have a “resistant” phenotype. Using F1 and F2 crosses of these two strains, we concluded that the susceptible CAI phenotype is autosomal recessive and… Advisors/Committee Members: Jordan, Michael (Committee Chair).

Subjects/Keywords: Immunology; hemophagocytic lymphohistiocytosis; macropinocytosis; tethering; macrophages

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APA (6^th Edition):

Zoller, E. (2011). Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis. (Doctoral Dissertation). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312483784

Chicago Manual of Style (16^th Edition):

Zoller, Erin. “Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis.” 2011. Doctoral Dissertation, University of Cincinnati. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312483784.

MLA Handbook (7^th Edition):

Zoller, Erin. “Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis.” 2011. Web. 17 Jan 2021.

Vancouver:

Zoller E. Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis. [Internet] [Doctoral dissertation]. University of Cincinnati; 2011. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312483784.

Council of Science Editors:

Zoller E. Mechanisms of consumptive anemia of inflammation: Roles for interferon-gamma and hemophagocytosis. [Doctoral Dissertation]. University of Cincinnati; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1312483784

20. Chabaud, Mélanie. Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques.

Degree: Docteur es, Biologie cellulaire, 2014, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2014PA05T021

►

Les cellules dendritiques (DCs) patrouillent les tissus périphériques à la recherche de dangers potentiels en se déplaçant à travers les tissus et en incorporant de… (more)

▼

Les cellules dendritiques (DCs) patrouillent les tissus périphériques à la recherche de dangers potentiels en se déplaçant à travers les tissus et en incorporant de grande quantité de matériel extracellulaire. Cet événement précoce de la réponse immunitaire adaptative est susceptible de déterminer l'amplitude et la qualité de l'activation des lymphocytes T et B. De ce fait, les DCs pourraient avoir besoin d'orchestrer leur motilité et leur fonction de capture des antigènes afin d'initier un réponse immunitaire efficace et adaptée. Afin d'étudier les mécanismes responsables de l'optimisation de l'échantillonnage des tissus par les DCs, nous avons suivi leur migration et leur capacité à capturer des antigènes dans des chambres micro-fluidiques contenant des canaux étroits qui permettent de reproduire l'espace confiné des tissus périphériques. De manière surprenante, nous avons découvert que la migration des DCs et leur aptitude à accumuler des antigènes sont des fonctions antagonistes et dépendent de l'activité du moteur moléculaire Myosine II. Nous avons observé que les DCs se déplacent en alternant des phases rapides au cours desquelles la Myosine II est distribuée de manière asymétrique à l'arrière des cellules, et des phases plus lentes pendant lesquelles la Myosine II est enrichie à l'avant. Les enrichissements transitoires de Myosine II à l'avant des DCs dépendent de l'association de la Myosine II avec la chaîne invariante associée au CMH-II (Ii). Ces évenements favorisent l'absorption d'antigènes et leur transport dans les compartiments endolysosomaux. Des expériences menées avec une pince optique nous ont permis de montrer que l'activité de la Myosine II à l'avant des cellules génère des forces mécaniques qui induisent le transport des vésicules vers l'intérieur de la cellule, probablement en modulant le flux rétrograde d'actine. Ainsi, au cours de cette thèse, nous avons montré que la Myosine II était nécessaire à la fois pour la migration cellulaire et la capture d'antigènes, établissant un mécanisme moléculaire qui permet de coordonner ces deux processus dans le temps et l'espace. Nous proposons que l'alternance de phases de haute mobilité et de phases d'arrêt associées à la capture d'antigènes confère aux DCs une stratégie de recherche intermittente qui leur permettrait d'optimiser la surveillance des tissus périphériques.

Dendritic cells (DCs) patrol peripheral tissues in search for potential dangers by actively crawling and internalizing extracellular materiel. This initial event of an adaptive immune response is likely to determine the magnitude and quality of T cell and B cell immunity. Therefore, DCs might need to tightly orchestrate their migration and their antigen uptake function in order to mount an efficient and adapted immune response. To investigate the mechanisms responsible for the optimization of tissues sampling by DCs, we monitored their migration and their ability to capture antigens in micro-fluidic chambers containing narrow channels that mimic the confined space of peripheral…

Advisors/Committee Members: Lennon-Dumenil, Ana-Maria (thesis director), Piel, Matthieu (thesis director).

Subjects/Keywords: Migration cellulaire; Macropinocytose; Myosine II; Chaine Invariante (CD74); Trafic endocytique; Capture d'antigènes; Cellules dendritiques; Cell Migration; Macropinocytosis; Myosin II; Invariant Chain (CD74); Endocytic trafficking; Antigen capture; Dendritic cells; 571.964 5

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

APA (6^th Edition):

Chabaud, M. (2014). Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2014PA05T021

Chicago Manual of Style (16^th Edition):

Chabaud, Mélanie. “Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques.” 2014. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed January 17, 2021. http://www.theses.fr/2014PA05T021.

MLA Handbook (7^th Edition):

Chabaud, Mélanie. “Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques.” 2014. Web. 17 Jan 2021.

Vancouver:

Chabaud M. Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2014. [cited 2021 Jan 17]. Available from: http://www.theses.fr/2014PA05T021.

Council of Science Editors:

Chabaud M. Cell migration and antigen uptake are two antagonistic functions that are coupled by Myosin II in dendritic cells : La migration cellulaire et la capture d'antigènes sont des fonctions antagonistes couplées par la Myosine II dans les cellules dendritiques. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2014. Available from: http://www.theses.fr/2014PA05T021

Texas Medical Center

21. Maxwell, Kelsey. Nanoscale Organization of the Small GTPase Rac1.

Degree: PhD, 2018, Texas Medical Center

URL: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/851

► Rac1 is a small, guanine-nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate actin-mediated motility, migration, and adhesion.… (more)

Subjects/Keywords: Rac1; Electron Microscopy; Nanoclusters; GTPase; Plasma membrane; Lipids; Phosphatidic acid; PIP3; Macropinocytosis; Polybasic domain; Biochemistry; Biophysics; Medicine and Health Sciences; Molecular Biology

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

APA (6^th Edition):

Maxwell, K. (2018). Nanoscale Organization of the Small GTPase Rac1. (Doctoral Dissertation). Texas Medical Center. Retrieved from https://digitalcommons.library.tmc.edu/utgsbs_dissertations/851

Chicago Manual of Style (16^th Edition):

Maxwell, Kelsey. “Nanoscale Organization of the Small GTPase Rac1.” 2018. Doctoral Dissertation, Texas Medical Center. Accessed January 17, 2021. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/851.

MLA Handbook (7^th Edition):

Maxwell, Kelsey. “Nanoscale Organization of the Small GTPase Rac1.” 2018. Web. 17 Jan 2021.

Vancouver:

Maxwell K. Nanoscale Organization of the Small GTPase Rac1. [Internet] [Doctoral dissertation]. Texas Medical Center; 2018. [cited 2021 Jan 17]. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/851.

Council of Science Editors:

Maxwell K. Nanoscale Organization of the Small GTPase Rac1. [Doctoral Dissertation]. Texas Medical Center; 2018. Available from: https://digitalcommons.library.tmc.edu/utgsbs_dissertations/851

22. Fletcher, Katherine Anne. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.39081 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774745

► Autophagy is a well-studied catabolic process through which cytoplasmic components are targeted for lysosomal degradation by autophagosomes. A key step in this process is the… (more)

▼ Autophagy is a well-studied catabolic process through which cytoplasmic components are targeted for lysosomal degradation by autophagosomes. A key step in this process is the recruitment, processing and lipidation of LC3 to autophagosomes. Recently it has become increasingly apparent that, through the unconventional use of some autophagy related proteins, LC3 can also become lipidated to distinct non-autophagosomal membranes of the endolysosomal system. This process is termed non-canonical autophagy and occurs independently of conventional autophagy initiation signals. Non-canonical autophagy usually occurs after macro endocytic engulfment events such as macropinocytosis, entosis and LC3 associated phagocytosis (LAP). Certain ionophores and lysosomotropic drugs, such as monensin, can also activate this process and promote LC3 lipidation to lysosomes. This project focuses on Atg16L1, an essential autophagy protein that directs the membrane site where LC3 is lipidated. Atg16L1 is relatively well characterised in autophagy but little is known about the mechanisms underlying its role in non-canonical autophagy. This project used a structure/function approach to assess the importance of different domains of Atg16L1 in the context of autophagy versus non-canonical autophagy. I have demonstrated for the first time, that the Atg16L1 C-terminal WD40 domain (CTD) is dispensable for its role in autophagy but essential for LC3 lipidation during non-canonical autophagy. Furthermore, single point mutants were uncovered in the CTD of Atg16L1 that likewise are dispensable for autophagy but fundamental to LC3 lipidation in non-canonical autophagy. These data provide a novel strategy for dissecting canonical and non-canonical autophagy pathways at a molecular level. This project used an existing mouse model with an Atg16L1 truncation (lacking the CTD and nearby residues) and implicated the lack of non canonical autophagy to a defect in MHCII antigen presentation. Furthermore this project has generated new refined Atg16L1 mutant models ablating non-canonical autophagy without affecting canonical autopahgy. In parallel, proteomic analysis was done to provide mechanistic insights into Atg16L1 binding partners in the context of non-canonical autophagy.

Subjects/Keywords: autophagy; non-canonical autophagy; LC3 associated phagocytosis; macropinocytosis

…after macroendocytic engulfment events such as macropinocytosis, entosis and LC3 associated…

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APA (6^th Edition):

Fletcher, K. A. (2019). Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.39081 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774745

Chicago Manual of Style (16^th Edition):

Fletcher, Katherine Anne. “Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.” 2019. Doctoral Dissertation, University of Cambridge. Accessed January 17, 2021. https://doi.org/10.17863/CAM.39081 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774745.

MLA Handbook (7^th Edition):

Fletcher, Katherine Anne. “Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy.” 2019. Web. 17 Jan 2021.

Vancouver:

Fletcher KA. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Jan 17]. Available from: https://doi.org/10.17863/CAM.39081 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774745.

Council of Science Editors:

Fletcher KA. Novel mechanisms of Atg16L1 recruitment in non-canonical autophagy. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.39081 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774745

23. Chung, Jun-Jae. Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids.

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

URL: https://openscholarship.wustl.edu/etd/1293

► I. Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. In nephrotic… (more)

▼ I. Podocytes are specialized epithelial cells in the kidney glomerulus that play important structural and functional roles in maintaining the filtration barrier. In nephrotic syndrome, a major breakdown of the kidney filtration barrier associated with proteinuria, hyperlipidemia, and edema, podocytes undergo changes in morphology and appear to internalize serum proteins. We postulated that fluid-phase uptake by podocytes might play a role in maintaining the integrity of the filtration barrier. Using fluid-phase tracers, we show that podocytes in vivo actively internalize fluid from the serum and that the rate of internalization is enhanced when the filtration barrier is disrupted. In vitro experiments demonstrated that lipids associated with serum albumin stimulate macropinocytosis in podocytes. This process was specific to podocytes as known stimuli that induce macropinocytosis in other cells had no effect on podocytes, while serum lipids did not stimulate macropinocytosis in other cells. A candidate lipid approach showed that certain unsaturated free fatty acids stimulate macropinocytosis through G protein coupled receptors, FFAR1, FFAR2 and FFAR3 and the Gβ/Gγ complex. Meanwhile, long-chain fatty acids were found to induce apoptosis in podocytes. These results suggest that podocytes sense the disruption of the filtration barrier via free fatty acids carried by albumin and respond to the increased protein by enhancing fluid-phase uptake. However, alterations in free fatty acids to albumin ratio during nephrotic syndrome may lead to dysregulation of macropinocytosis and podocyte toxicity and play an important role in the development of podocyte diseases. II. The early events that initiate inflammation in the adipose tissue during obesity are not well defined. It is unclear whether the recruitment of CD8 T cells to the adipose tissue during onset of obesity occurs through antigen-dependent or -independent processes. We have previously shown that interaction between NKG2D (natural-killer group 2, member D) and its ligand Rae-1ɛ is sufficient to recruit cytotoxic T lymphocytes to the pancreas and induce insulitis. Here, we tested to see whether NKG2D-NKG2D ligand interaction is also involved in obesity-induced adipose tissue inflammation and insulin resistance. We observed a significant induction of NKG2D ligand expression in the adipose tissue of obese mice, especially during the early stages of obesity. However, mice lacking NKG2D developed similar levels of insulin resistance and adipose tissue inflammation compared to control mice when placed on a high fat diet. Moreover, overexpression of Rae-1ɛ in the adipose tissue did not increase immune cell infiltration to the adipose tissue neither in the setting of a normal or high fat diet. These results indicate that, unlike in the pancreas, NKG2D-NKG2D ligand interaction does not play a critical role in obesity-induced inflammation in the adipose tissue. Advisors/Committee Members: Andrey S Shaw.

Subjects/Keywords: Free fatty acids; Inflammation; Macropinocytosis; NKG2D; Obesity; Podocytes

…albumin stimulate macropinocytosis in podocytes. This process was specific to podocytes as known… …stimuli that induce macropinocytosis in other cells had no effect on podocytes, while xiii… …serum lipids did not stimulate macropinocytosis in other cells. A candidate lipid approach… …showed that certain unsaturated free fatty acids stimulate macropinocytosis through G protein… …macropinocytosis and podocyte toxicity and play an important role in the development of podocyte diseases…

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APA (6^th Edition):

Chung, J. (2014). Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/etd/1293

Chicago Manual of Style (16^th Edition):

Chung, Jun-Jae. “Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids.” 2014. Doctoral Dissertation, Washington University in St. Louis. Accessed January 17, 2021. https://openscholarship.wustl.edu/etd/1293.

MLA Handbook (7^th Edition):

Chung, Jun-Jae. “Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids.” 2014. Web. 17 Jan 2021.

Vancouver:

Chung J. Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2014. [cited 2021 Jan 17]. Available from: https://openscholarship.wustl.edu/etd/1293.

Council of Science Editors:

Chung J. Regulation of Fluid-phase Uptake in Podocytes by Albumin-associated Lipids. [Doctoral Dissertation]. Washington University in St. Louis; 2014. Available from: https://openscholarship.wustl.edu/etd/1293

University of Toledo Health Science Campus

24. Kaul, Aparna. Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells.

Degree: PhD, College of Medicine, 2009, University of Toledo Health Science Campus

URL: http://rave.ohiolink.edu/etdc/view?acc_num=mco1243364096

► The concept of programmed cell death has evolved over the years to include bothapoptotic and non-apoptotic death mechanisms. This study describes a novel form ofnon-apoptotic… (more)

▼ The concept of programmed cell death has evolved over the years to include bothapoptotic and non-apoptotic death mechanisms. This study describes a novel form ofnon-apoptotic cell death induced as a result of dysregulated macropinocytosis. We havenamed this cell death “methuosis”. Methuosis is observed when the activated form of RasGTPase is over-expressed in glioblastoma cells. It is accompanied by the accumulation oflarge phase-lucent cytoplasmic vacuoles, followed by rounding up, detachment, anddisintegration of the cells. The vacuoles quickly take up extracellular fluid-phase tracers,a hallmark of macropinosomes. Our studies also show that the Ras-induced vacuoles arenot acidic and are negative for LC3-II (a marker for autophagosomes), transferrin andEEA1 (endosomal markers). These observations rule out the vacuoles originating fromautophagosomal, endosomal or lysosomal compartments. Even though caspase activationis observed in dying cells, death is not prevented by zVAD-fmk, a pan caspase inhibitor.Electron microscopy revealed that the dying cells did not show classical signs ofapoptosis, like chromatin condensation. These findings indicate that caspase activation isnot required for methuosis to occur. Studies performed to decipher the signalingpathway(s) stimulated by Ras revealed that methuosis does not depend on the activationof Raf kinase, PI-3K or RalGDS, the most well-studied Ras signaling intermediates.Interestingly, constitutively active Rac1 induces an identical vacuolar phenotype inglioblastoma cells. Rac1-induced vacuoles are also derived from macropinosomes. Wepostulate that activated Ras is stimulating Rac GTPase via a unique downstream effectorto initiate methuosis in glioblastoma cells.ER stress-initiated apoptosis has recently gained attention as an effective deathinducer in cancer cells. This work shows for the first time that the mechanism by whichcalphostin-C, a photoactivatable inhibitor of protein kinase C, induces apoptosis in cancercells involves ER stress. Calphostin-C potently reduces the viability of a number ofcancer cell lines, including glioblastomas. The cell death induced by cal-C involvesaccumulation of vacuoles derived from the ER with a concomitant block in the proteintrafficking from ER to Golgi. There is a rapid activation of ER stress markers, JNK,PERK, and the induction of pro-apoptotic protein CHOP. Activation of caspases-9 and 7,along with PARP cleavage, is observed following the activation of ER stress signaling.Our studies indicate that apoptosis induced by cal-C has a strong ER-stress componentand that this compound has a potential of being exploited as a chemotherapeutic agent forphotodynamic therapy. Advisors/Committee Members: Maltese, William (Committee Chair).

Subjects/Keywords: Cellular Biology; Molecular Biology; Apoptosis; methuosis; endoplasmic reticulum-stress; macropinocytosis; non-apoptotic; glioblastoma

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APA (6^th Edition):

Kaul, A. (2009). Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells. (Doctoral Dissertation). University of Toledo Health Science Campus. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=mco1243364096

Chicago Manual of Style (16^th Edition):

Kaul, Aparna. “Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells.” 2009. Doctoral Dissertation, University of Toledo Health Science Campus. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=mco1243364096.

MLA Handbook (7^th Edition):

Kaul, Aparna. “Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells.” 2009. Web. 17 Jan 2021.

Vancouver:

Kaul A. Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells. [Internet] [Doctoral dissertation]. University of Toledo Health Science Campus; 2009. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1243364096.

Council of Science Editors:

Kaul A. Mechanisms of Non-Conventional Cell Death in Brain Tumor Cells. [Doctoral Dissertation]. University of Toledo Health Science Campus; 2009. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1243364096

Kyoto University

25. Arafiles, Jan Vincent Valenzuela. Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action .

Degree: 2020, Kyoto University

URL: http://hdl.handle.net/2433/259021

Subjects/Keywords: macropinocytosis-inducing peptide; intracellular delivery; endosome escape; thiol-disulfide exchange reaction; dimerization

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

APA (6^th Edition):

Arafiles, J. V. V. (2020). Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action . (Thesis). Kyoto University. Retrieved from http://hdl.handle.net/2433/259021

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):

Arafiles, Jan Vincent Valenzuela. “Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action .” 2020. Thesis, Kyoto University. Accessed January 17, 2021. http://hdl.handle.net/2433/259021.

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

MLA Handbook (7^th Edition):

Arafiles, Jan Vincent Valenzuela. “Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action .” 2020. Web. 17 Jan 2021.

Vancouver:

Arafiles JVV. Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action . [Internet] [Thesis]. Kyoto University; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2433/259021.

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

Council of Science Editors:

Arafiles JVV. Macropinocytosis-Inducing Peptides: Identification, Utility, and Mechanism-of-Action . [Thesis]. Kyoto University; 2020. Available from: http://hdl.handle.net/2433/259021

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

26. Kostopoulou, Nikoleta. Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της.

Degree: 2015, University of Ioannina; Πανεπιστήμιο Ιωαννίνων

URL: http://hdl.handle.net/10442/hedi/42887

► TGF-β superfamily members regulate a wide range of biological processes, such as cell proliferation, differentiation, maintenance of pluripotency and angiogenesis. Activin A, a cytokine of… (more)

▼ TGF-β superfamily members regulate a wide range of biological processes, such as cell proliferation, differentiation, maintenance of pluripotency and angiogenesis. Activin A, a cytokine of TGF-β superfamily, binds to heterotetrameric complexes of type I and type II Ser/Thr kinase receptors and transduce signals through SMAD2 and SMAD3, promoting the transcription of target genes. In order to orchestrate diverse biological functions, signaling is tightly regulated, both spatially and temporally. The spatial organization and trafficking of ligand-receptor complexes is critical in signal transduction. Internalization of cargo proteins is carried out by various endocytic pathways, such as clathrin-dependent endocytosis, as well as clathrin-independent pathways. Sorting events initiated at early endosomes determine the fate of cargo, including signaling propagation, recycling to the plasma membrane or degradation. The target of our research was to investigate which endocytic routs internalize the complex of Activin-Receptors and the impact of trafficking events on Activin A signaling. Finally, since Activin A plays a prominent role in biology of human embryonic stem cells (hESCs), where signaling and trafficking events of Activin A/receptor complexes are mainly unknown, the current effort is to apply our knowledge to hESCs. Our first goal was to test which endocytic routs are utilized from Activin A-receptor complex on endothelial cells, and to address the role of known regulators of trafficking on Activin A signaling. We found that dynamin dependent routs, such as clathrin and caveolin dependent endocytosis, affect Activin A signaling. Knock down of clathrin and caveolin, significantly down regulated the phosphorylation of SMAD2/3, but it didn’t change the internalization of ActivinA-Alexa488. It seems that the main endocytic route for Activin A is macropinocytosis. ActivinA-Alexa488 colocalises with Detran-TexasRed and Rabankyrin-5 on large vesicles, with size bigger that 0,2 μm, defined as macropinosomes. Knock down of Rabankyrin-5 decreases the phosphorylation of SMAD2/3 and the internalization of ligand. The opposite effect caused the overexpression of this protein. These results are in agreement with those performed using know macropinocytosis inhibitors, such as EIPA, Cytochalasin D and LY249002. Also, Activin A induces macropinocytosis, since it upregulates Dextran-TexasRed uptake in HUVECs, and causes membrane ruffling and actin filaments reorganization. Additionally, we tried to apply our knowledge on stem cell lineages, repeating some key experiments. The results show that the regulation of Activin A signaling through endocytosis differs between pluripotent, multipotent and differentiated cells. Macropinocytosis is either absent or is not affecting Activin A signaling on stem cells. Taking advantage of a microarray analysis performed for our lab, we detected two phosphatases with distinct expression levels between the cell lines used, which are absent in pluripotent cells. These phosphatases are…

Subjects/Keywords: Ακτιβίνη Α; Υποδοχείς; Σηματοδότηση; Ενδοκυττάρωση; Μεμβρανική διακίνηση; Μακροπινοκυττάρωση; Κλαθρινο-εξαρτώμενη ενδοκυττάρωση; Ενδοθηλιακά κύτταρα; Ανθρώπινα βλαστικά κύτταρα; Activin A; Activin receptors; Signaling; Endocytosis; Μembrane trafficking; Macropinocytosis; Clathrin dependent endocytosis; Endothelial cells; Human embryonic stem cells

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

APA (6^th Edition):

Kostopoulou, N. (2015). Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της. (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/42887

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):

Kostopoulou, Nikoleta. “Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της.” 2015. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed January 17, 2021. http://hdl.handle.net/10442/hedi/42887.

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

MLA Handbook (7^th Edition):

Kostopoulou, Nikoleta. “Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της.” 2015. Web. 17 Jan 2021.

Vancouver:

Kostopoulou N. Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της. [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10442/hedi/42887.

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

Council of Science Editors:

Kostopoulou N. Ο ρόλος των πρωτεϊνών του συμπλέγματος των υποδοχέων της ακτιβίνης Α στη μεταγωγή του σήματος και τη βιολογική δραστικότητά της. [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2015. Available from: http://hdl.handle.net/10442/hedi/42887

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

27. Welliver, Timothy. Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis.

Degree: PhD, Immunology, 2011, University of Michigan

URL: http://hdl.handle.net/2027.42/86450

► In murine macrophages stimulated with Macrophage-Colony-stimulating Factor (M-CSF), signals essential to macropinosome formation are restricted to the domain of plasma membrane enclosed within cup-shaped, circular… (more)

Subjects/Keywords: Membrane Diffusion Barriers Localize Signal Amplification During Macropinocytosis; Microbiology and Immunology; Science

…an  important  immunological  process,  macropinocytosis.  The  general  finding  of  this… …macrophages  and  macropinocytosis,  with  a  focus  on  their  importance  to  the  immune  system… …origin  to  mature  effector.  The  discussion  on  macropinocytosis provides information on a… …Macropinocytosis  1.3.1 ��  Role of Macropinocytosis in Immunology    Macropinocytosis  is  best  known… …for  antigen  presentation.  Macropinocytosis,  then,  is  a  central  part  of  the  normal…

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

APA (6^th Edition):

Welliver, T. (2011). Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/86450

Chicago Manual of Style (16^th Edition):

Welliver, Timothy. “Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis.” 2011. Doctoral Dissertation, University of Michigan. Accessed January 17, 2021. http://hdl.handle.net/2027.42/86450.

MLA Handbook (7^th Edition):

Welliver, Timothy. “Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis.” 2011. Web. 17 Jan 2021.

Vancouver:

Welliver T. Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis. [Internet] [Doctoral dissertation]. University of Michigan; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2027.42/86450.

Council of Science Editors:

Welliver T. Membrane Diffusion Barriers Localize Signal Amplification during Macropinocytosis. [Doctoral Dissertation]. University of Michigan; 2011. Available from: http://hdl.handle.net/2027.42/86450

28. Goula, Evangeli. Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα.

Degree: 2019, University of Ioannina; Πανεπιστήμιο Ιωαννίνων

URL: http://hdl.handle.net/10442/hedi/46232

►

So far, endocytosis induced signaling as well as signaling induced exocytosis have been studied separately. Thus, it remains unknown whether endocytosis and exocytosis are interdependent… (more)

▼

So far, endocytosis induced signaling as well as signaling induced exocytosis have been studied separately. Thus, it remains unknown whether endocytosis and exocytosis are interdependent processes and which are the basic molecular mechanisms of this relationship? In the present study, the inhibitors dyngo-4a (for clathrin-dependent endocytosis) and EIPA (for macropinocytosis) were used to block the different internalization routes of VEGFR2 and the consequences of this inhibition on WPBs exocytosis were tested. The results demonstrate that clathrin-dependent endocytosis of VEGFR2 causes a minor inhibition on the percentage of secreted vWF, as compared to macropinocytosis, which has the predominant inhibitory role. The inhibitory role of macropinocytosis on VEGF-induced WPBs exocytosis was also tested by siRNAs treatments of common regulatory proteins of the macropinocytosis route (Rabankyrin-5, CDC42), followed by assessment of the secreted vWF by an ELISA-based method. Indeed, siRNAs treatment of the above proteins, individually or in combination, increased the VEGF-induced WPBs exocytosis. In addition, time-lapse confocal video microscopy in HUVECs suggests that upon VEGF stimulation, VEGFR2 positive endosomes are in limited contact with WPBs. In order to better understanding of the molecular mechanisms responsible for VEGF-induced exocytosis of WPBs, we employed a proteomic analysis of the secreted proteins in activated endothelial cells. Among the secreted proteins which were analyzed by high resolution mass spectrometry (nLC-MS/MS) was the galectin-1 protein (Gal-1). In the present study we found that galectin-1 is targeted to the WPBs of endothelial cells, since confocal microscopy (LSCM/CLSM) with/or STED demonstrates that galectin-1 co-localizes with vWF, the main cargo molecule of WPBs. This observation was also confirmed by its co-localization with other bona fide markers of WPBs (P-selectin, Rab27a, Rab3a, Rab3d). Surprisingly, galectin-1 was found only in a subset of WPBs and in a “rare” subpopulation of HUVECs. The results show that, upon VEGF/bFGF/ATP induction galectin-1 is localized in WPBs that recapture the extracellular anti-vWF antibodies, thus undergo "kiss-and-run" exocytosis. In parallel, internalization assays of recombinant galectin-1 proteins added extracellularly in culture medium, in control and siRNA treated for galectin-1 HUVECs, show that recombinant galectin-1 is localized in a limited number of WPBs. In addition, removal of extracellular galectin-1 from the culture medium reduces the number of galectin-1 positive WPBs significantly. The above data provide novel insights into the mechanism of unconventional secretion of galectin-1, implying that its secretion is partly, due to “kiss-and-run” exocytosis of WPBs.

Μέχρι στιγμής, η επαγόμενη από την ενδοκυττάρωση σηματοδότηση καθώς και η σηματοδοτούμενη εξωκυττάρωση έχουν μελετηθεί ξεχωριστά. Έτσι, δεν γνωρίζουμε αν η ενδοκυττάρωση και η εξωκυττάρωση είναι αλληλοεξαρτώμενες διαδικασίες και ποιοι είναι οι βασικοί μοριακοί μηχανισμοί…

Subjects/Keywords: Ενδοκυττάρωση; Μακροπινοκυττάρωση; Σηματοδότηση του VEGFR2; Εξωκυττάρωση; UPS (μη συμβατική πρωτεϊνική έκκριση); Ενδοθηλιακά κύτταρα; Endocytosis; Macropinocytosis; VEGFR2 signaling; Weibel-palade bodies; Exocytosis; UPS (unconventional protein secretion); Galectin-1; Gal-1; Endothelial cells

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

APA (6^th Edition):

Goula, E. (2019). Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα. (Thesis). University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Retrieved from http://hdl.handle.net/10442/hedi/46232

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):

Goula, Evangeli. “Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα.” 2019. Thesis, University of Ioannina; Πανεπιστήμιο Ιωαννίνων. Accessed January 17, 2021. http://hdl.handle.net/10442/hedi/46232.

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

MLA Handbook (7^th Edition):

Goula, Evangeli. “Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα.” 2019. Web. 17 Jan 2021.

Vancouver:

Goula E. Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα. [Internet] [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2019. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10442/hedi/46232.

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

Council of Science Editors:

Goula E. Χωροχρονική οργάνωση και μηχανισμοί επικοινωνίας μεταξύ ενδοκυττάρωσης και ρυθμιζόμενης έκκρισης κατά τη σηματοδότηση του VEGFR2 στα ενδοθηλιακά κύτταρα. [Thesis]. University of Ioannina; Πανεπιστήμιο Ιωαννίνων; 2019. Available from: http://hdl.handle.net/10442/hedi/46232

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

University of Queensland

29. Qi, Xiaying. The role of sorting nexins in macropinocytosis and Salmonella invasion.

Degree: Institute for Molecular Bioscience, 2015, University of Queensland

URL: http://espace.library.uq.edu.au/view/UQ:371851

Subjects/Keywords: Macropinocytosis; Sorting nexin (SNX); S. Typhimurium; Phosphoinositides; 060108 Protein Trafficking; 060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics)

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

APA (6^th Edition):

Qi, X. (2015). The role of sorting nexins in macropinocytosis and Salmonella invasion. (Thesis). University of Queensland. Retrieved from http://espace.library.uq.edu.au/view/UQ:371851

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):

Qi, Xiaying. “The role of sorting nexins in macropinocytosis and Salmonella invasion.” 2015. Thesis, University of Queensland. Accessed January 17, 2021. http://espace.library.uq.edu.au/view/UQ:371851.

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

MLA Handbook (7^th Edition):

Qi, Xiaying. “The role of sorting nexins in macropinocytosis and Salmonella invasion.” 2015. Web. 17 Jan 2021.

Vancouver:

Qi X. The role of sorting nexins in macropinocytosis and Salmonella invasion. [Internet] [Thesis]. University of Queensland; 2015. [cited 2021 Jan 17]. Available from: http://espace.library.uq.edu.au/view/UQ:371851.

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

Council of Science Editors:

Qi X. The role of sorting nexins in macropinocytosis and Salmonella invasion. [Thesis]. University of Queensland; 2015. Available from: http://espace.library.uq.edu.au/view/UQ:371851

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

30. Feliciano, William David. Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis.

Degree: PhD, Cellular & Molecular Biology, 2011, University of Michigan

URL: http://hdl.handle.net/2027.42/89652

► Infection by Listeria monocytogenes involves escape from its phagocytic compartment prior to fusion with the lysosome. Previous studies show that small GTPase Rab5a plays a… (more)

▼ Infection by Listeria monocytogenes involves escape from its phagocytic compartment prior to fusion with the lysosome. Previous studies show that small GTPase Rab5a plays a crucial role in Lm ability to escape from its compartment and that Lm is able to modulate Rab5a activity, promoting GDP exchange of Rab5a. Rab5a regulates the homo- and heterotypic fusion of membranous organelles during the early stages of endocytosis. The extent to which molecules that regulate Rab5a coordinate its cycling on membranes to affect the behavior of individual organelles has not been determined. This study used novel Förster Resonance Energy Transfer (FRET) microscopic methods to analyze the Rab5a cycle on macropinosomes and phagosomes, two large endocytic vesicles that form in ruffled regions of cell membranes. In Cos-7 cells and mouse macrophages stimulated with growth factors, Rab5a activation followed immediately after its recruitment to newly formed macropinosomes. Rab5a activity increased continuously and uniformly over macropinosome membranes then decreased continuously, with Rab5a deactivation preceding dissociation by 1-12 min. Maximal levels of Rab5a activity were independent of organelle size, but Rab5a cycles were longer on larger macropinosomes, consistent with an integrative activity governing Rab5a dynamics on individual organelles. The Rab5a cycle was destabilized by microtubule depolymerization and by bafilomycin A1. Overexpression of activating and inhibitory proteins indicated that active Rab5a stabilized macropinosomes. Thus, overall Rab5a activity on macropinosomes is coordinated by macropinosome structure and physiology. In macrophages Rab5a showed different levels of FRET on Lm-containing vacuoles. Macropinosomes that formed secondary to the phagocytic events showed higher FRET levels than during RBC and Lm phagocytosis. During uptake of hly- and heat-killed Lm, Rab5a localized to the vacuole with low FRET levels, which points to a possible role of LLO. During vesicle fusion events Rab5a FRET was higher at the point of contact of the vacuoles and increased over the whole organelle after fusion implying two distinct regulatory events. Thus, as on macropinosomes Rab5a plays a role in phagocytosis but requires lower levels of activation. Lm affects Rab5a activation cycling although currently we are not able to elucidate if Lm vacuoles with low FRET levels have higher survival rates. Advisors/Committee Members: Swanson, Joel A. (committee member), Fuller, Robert S. (committee member), Nielsen, Erik E. (committee member), Verhey, Kristen J. (committee member), Weisman, Lois (committee member).

Subjects/Keywords: Rab5; FRET Stoichiometry; Macropinocytosis; Phagocytosis; Listeria Monocytogenes; Ratiometric Microscopy; Microbiology and Immunology; Molecular, Cellular and Developmental Biology; Science (General); Science

…Macropinocytosis Macropinocytosis is the mechanism by which cells internalize large volumes of… …macropinocytosis when stimulated with macrophage colony-stimulating factor (M-CSF) or with… …induced macropinocytosis depends on Rac1 and the Rac1-binding protein WAVE2 (4). Rac1… …the membrane by phosphorylation of CtBP1/Bars during macropinocytosis (5). Cdc42… …and Arf6 also play important roles during macropinocytosis in macrophages, affecting actin…

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

APA (6^th Edition):

Feliciano, W. D. (2011). Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/89652

Chicago Manual of Style (16^th Edition):

Feliciano, William David. “Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis.” 2011. Doctoral Dissertation, University of Michigan. Accessed January 17, 2021. http://hdl.handle.net/2027.42/89652.

MLA Handbook (7^th Edition):

Feliciano, William David. “Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis.” 2011. Web. 17 Jan 2021.

Vancouver:

Feliciano WD. Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis. [Internet] [Doctoral dissertation]. University of Michigan; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2027.42/89652.

Council of Science Editors:

Feliciano WD. Regulation of Rab5 Activation Cycle during Macropinocytosis and Phagocytosis. [Doctoral Dissertation]. University of Michigan; 2011. Available from: http://hdl.handle.net/2027.42/89652

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Open Access Theses and Dissertations