Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 47, Pages 18958-18963Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1311135110
Keywords
seamless tubule; contractility; soft lithography
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Funding
- Beckman Young Investigator Award
- Hellman Family New Faculty Award
- National Institutes of Health EUREKA [GM094798]
- University of California Cancer Research Coordinating Committee
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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.
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