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The role of Rab19 as a regulator of the nuclear envelope-associated endosomal pathway
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Shah, Poonam (2022) The role of Rab19 as a regulator of the nuclear envelope-associated endosomal pathway. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3869826
Abstract
The Nucleus-Associated Endosome (NAE) pathway is an endocytic trafficking pathway that provides a direct link from the plasma membrane to the nucleus of the cell. This study describes the development of a siRNA-based high-content imaging assay for the identification of regulators in the NAE pathway, using Pseudomonas Exotoxin A (PE), a cargo molecule that translocates to the nucleus, as a marker for NAE. Rab19, a member of the Rab GTPase family, was identified as a key player in the NAE pathway as knockdown of Rab19 resulted in a significant reduction in the number of PE-laden vesicles at the nucleus. High-resolution microscopy revealed that GFP-Rab19 localises to intracellular vesicles and the nuclear envelope, leading to the hypotheses that Rab19 functions at the vesicular level (NAE formation or translocation) or at the level of the nucleus (NAE docking or fusion). Rab19 vesicles were observed associated with large EEA1-positive early endosomes. Rab19-positive vesicular structures, containing PE, were also observed at the nuclear envelope. These structures were similar in size to the Rab19 vesicles associated with early endosomes. We propose a model that could explain the function of Rab19 in the NAE Pathway: Rab19 vesicles bud off from early endosomes and carry PE from the early endosome to the nucleus in NAE. The Rab19-vesicles then dock and fuse with the Rab19-positive nuclear envelope. Whether Rab19 is also required at the nuclear envelope to facilitate NAE docking requires further investigation.
Item Type: | Thesis (PhD) | ||||
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Subjects: | Q Science > QH Natural history Q Science > QH Natural history > QH426 Genetics |
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Library of Congress Subject Headings (LCSH): | Endosomes, Pseudomonas, Nuclear membranes, Endocytosis | ||||
Official Date: | January 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Royle, Stephen J. ; Bard, Fred | ||||
Sponsors: | Singapore. Agency for Science, Technology and Research ; University of Warwick | ||||
Format of File: | |||||
Extent: | 163 pages : illustrations | ||||
Language: | eng |
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