Fletcher, Sarah Jane (2013). Investigating the role of vesicle trafficking in epithelial cell migration. University of Birmingham. Ph.D.
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Fletcher13PhD.pdf
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Abstract
Cell migration is required for re-epithelialisation following wounding. Vesicle trafficking is widely implicated in regulating cell migration. The scratch-wound healing assay was utilised to determine mechanistic linkages between endocytosis and migration in the Madin-Darby canine kidney (MDCK) epithelial cell line. These studies demonstrate clathrin-mediated, dynamin-dependent and caveolar endocytosis, Rab4- and Rab11-mediated trafficking are required for effective wound closure. Furthermore, it identifies caveolar endocytosis polarised to the cell rear, whilst exocytosis of vesicles derived from the Rab11 and Rab25 trafficking pathways was not polarised during epithelial wound healing. Additionally, although the dynamin-dependent endocytosis pathways do have a function in MDCK cell migration it is not through regulation of focal adhesion (FA) turnover. Alternatively, these studies demonstrated clathrin-mediated endocytosis of the tight junction (TJ) protein occludin from the wound edge to Rab5 positive endosomal compartments shortly following wounding, as a novel mechanism for regulating cell motility. However, little is known about occludin trafficking under non-stimulated conditions, therefore this novel study demonstrates occludin undergoes continuous biosynthetic secretory and endocytic degradative trafficking. These findings are important as regulation of TJ structure is integral in maintenance of epithelial membranes, whilst loss of cell-cell junctions is a hallmark of epithelial mesenchymal transition (EMT) during cancer metastasis. Therefore this work demonstrates a clear link between regulation of TJ proteins and directed epithelial cell migration.
| Type of Work: | Thesis (Doctorates > Ph.D.) | ||||||
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| Award Type: | Doctorates > Ph.D. | ||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences | ||||||
| School or Department: | School of Biosciences | ||||||
| Funders: | None/not applicable | ||||||
| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/4029 |
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