科研之友
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摘要
Maintaining cell cohesiveness within tissues requires that intercellular adhesions develop sufficient strength to support traction forces applied by myosin motors and by neighboring cells. Cadherins are transmembrane receptors that mediate intercellular adhesion. The cadherin cytoplasmic domain recruits several partners, including catenins and vinculin, at sites of cell-cell adhesion. Our study used force measurements to address the role of alpha E-catenin and vinculin in the regulation of the strength of E-cadherin-based adhesion. alpha E-catenin-deficient cells display only weak aggregation and fail to strengthen intercellular adhesion over time, a process rescued by the expression of alpha E-catenin or chimeric E-cadherin center dot alpha E-catenins, including a chimera lacking the alpha E-catenin dimerization domain. Interestingly, an alpha E-catenin mutant lacking the modulation and actin-binding domains restores cadherin-dependent cell-cell contacts but cannot strengthen intercellular adhesion. The expression of alpha E-catenin mutated in its vinculin-binding site is defective in its ability to rescue cadherin-based adhesion strength in cells lacking alpha E-catenin. Vinculin depletion or the overexpression of the alpha E-catenin modulation domain strongly decreases E-cadherin-mediated adhesion strength. This supports the notion that both molecules are required for intercellular contact maturation. Furthermore, stretching of cell doublets increases vinculin recruitment and alpha 18 anti-alpha E-catenin conformational epitope immunostaining at cell-cell contacts. Taken together, our results indicate that alpha E-catenin and vinculin cooperatively support intercellular adhesion strengthening, probably via a mechanoresponsive link between the E-cadherin beta-catenin complexes and the underlying actin cytoskeleton.
- 出版日期2013-2-15
