Self-contact elimination by membrane fusion

Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18958-63. doi: 10.1073/pnas.1311135110. Epub 2013 Nov 4.

Abstract

Mutual, homophilic cell-cell adhesion between epithelial cells is required for proper maintenance of epithelial barrier function. Whereas opposing membranes from neighboring cells rapidly assemble junctional complexes, self-contacting membranes curiously do not, suggesting that cells have the ability to prevent the maturation of self-junctions. Using a self-contact-inducing microfabricated substrate, we show that self-contacts of normal epithelial cells are rapidly eliminated by membrane fusion between two opposing plasma membranes of a single cell. This membrane fusion is most frequently observed in E-cadherin-expressing epithelial cells, but not in fibroblasts. The efficiency of self-contact elimination depends on extracellular calcium concentration and the level of E-cadherin, suggesting that E-cadherin, although not required, enhances membrane fusion efficiency by bringing opposing membranes into close apposition to one another. Additionally, Rho-associated protein kinase inhibition decreases self-contact-induced membrane fusion of epithelial cells, suggesting that this fusion may be mechanically regulated through the actin-myosin network. This self-contact-induced membrane fusion is a key elimination mechanism for unwanted self-junctions and may be a feature of cell self-recognition.

Keywords: contractility; seamless tubule; soft lithography.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cadherins / metabolism*
  • Dogs
  • Epithelial Cells / physiology*
  • Humans
  • Intercellular Junctions / physiology
  • MCF-7 Cells
  • Madin Darby Canine Kidney Cells
  • Membrane Fusion / physiology*
  • Mice
  • Microscopy, Confocal
  • Oligonucleotides / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Cadherins
  • Oligonucleotides
  • rho-Associated Kinases