Clathrin-mediated endocytosis regulates occludin, and not focal adhesion, distribution during epithelial wound healing

Sarah J. Fletcher, Natalie S. Poulter, Elizabeth J. Haining, Joshua Z. Rappoport*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background information: Vesicle trafficking has long been suggested to play mechanistic roles in regulating directed cell migration. Recent evidence demonstrates that specific cell types and modes of migration involve transport of particular cargo through particular pathways. Epithelial wound healing is essential in tissue repair. However, investigations into the mechanisms regulating cell migration have mainly focused upon other models such as fibroblast-derived cells. Roles for vesicle trafficking pathways in regulating directed cell migration have been identified in recent studies, but mechanisms through which endocytosis might be involved in epithelial wound healing have not been as well studied. Therefore, we analysed potential regulatory roles for endocytosis pathways during epithelial cell motility, with a particular focus on cell adhesion. Results: Specifically, and in contrast to studies in fibroblasts, we find no evidence for a link between endocytosis and the distribution of focal adhesions. However, the localisation of occludin, an essential component of tight junctions, is regulated through endocytosis. We identified epithelial monolayer wounding as a stimulus for endocytosis of occludin and have shown that internalisation of occludin from the wound edge occurs through clathrin-mediated endocytosis (CME) into a rab5-positive compartment. Conclusions: Thus, these studies have evaluated mechanistic roles for dynamin-dependant, CME and caveolar endocytosis during epithelial wound healing and have provided contrasting observations between analyses of cell motility in fibroblast models and epithelial cells. In conclusion, these studies have identified a novel mechanism for regulation of occludin during wound healing.

Original languageEnglish (US)
Pages (from-to)238-256
Number of pages19
JournalBiology of the Cell
Volume104
Issue number4
DOIs
StatePublished - Apr 1 2012

Keywords

  • Cell adhesion
  • Cell migration
  • Endocytosis/exocytosis

ASJC Scopus subject areas

  • Cell Biology

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