Regulation of cell-cell adhesion by the cadherin-catenin complex.

Ca(2+)-dependent cell-cell adhesion is regulated by the cadherin family of cell adhesion proteins. Cadherins form trans-interactions on opposing cell surfaces which result in weak cell-cell adhesion. Stronger cell-cell adhesion occurs by clustering of cadherins and through changes in the organization of the actin cytoskeleton. Although cadherins were thought to bind directly to the actin cytoskeleton through cytoplasmic proteins, termed alpha- and beta-catenin, recent studies with purified proteins indicate that the interaction is not direct, and instead an allosteric switch in alpha-catenin may mediate actin cytoskeleton reorganization. Organization and function of the cadherin-catenin complex are additionally regulated by phosphorylation and endocytosis. Direct studies of cell-cell adhesion has revealed that the cadherin-catenin complex and the underlying actin cytoskeleton undergo a series of reorganizations that are controlled by the Rho GTPases, Rac1 and RhoA, that result in the expansion and completion of cell-cell adhesion. In the present article, in vitro protein assembly studies and live-cell studies of de novo cell-cell adhesion are discussed in the context of how the cadherin-catenin complex and the actin cytoskeleton regulate cell-cell adhesion.