(alpha)-Catenin Is a Molecular Switch that Binds E-Cadherin-(beta)-Catenin and Regulates Actin-Filament Assembly

Epithelial cell-cell junctions, organized by adhesion proteins and the underlying actin cytoskeleton, are considered to be stable structures maintaining the structural integrity of tissues. Contrary to the idea that (alpha)-catenin links the adhesion protein E-cadherin through (beta)-catenin to the actin cytoskeleton, in the accompanying paper we report that (alpha)-catenin does not bind simultaneously to both E-cadherin-(beta)-catenin and actin filaments. Here we demonstrate that (alpha)-catenin exists as a monomer or a homodimer with different binding properties. Monomeric (alpha)-catenin binds more strongly to E-cadherin-(beta)-catenin, whereas the dimer preferentially binds actin filaments. Different molecular conformations are associated with these different binding states, indicating that (alpha)-catenin is an allosteric protein. Significantly, (alpha)-catenin directly regulates actin-filament organization by suppressing Arp2/3-mediated actin polymerization, likely by competing with the Arp2/3 complex for binding to actin filaments. These results indicate a new role for (alpha)-catenin in local regulation of actin assembly and organization at sites of cadherin-mediated cellcell adhesion.