Biochemical and structural analysis of α-catenin in cell–cell contacts

Abstract

Cadherins are transmembrane adhesion molecules that mediate homotypic cell–cell contact. In adherens junctions, the cytoplasmic domain of cadherins is functionally linked to the actin cytoskeleton through a series of proteins known as catenins. E-cadherin binds to β-catenin, which in turn binds to α-catenin to form a ternary complex. α-Catenin also binds to actin, and it was assumed previously that α-catenin links the cadherin–catenin complex to actin. However, biochemical, structural and live-cell imaging studies of the cadherin–catenin complex and its interaction with actin show that binding of β-catenin to α-catenin prevents the latter from binding to actin. Biochemical and structural data indicate that α-catenin acts as an allosteric protein whose conformation and activity changes depending on whether or not it is bound to β-catenin. Initial contacts between cells occur on dynamic lamellipodia formed by polymerization of branched actin networks, a process controlled by the Arp2/3 (actin-related protein 2/3) complex. α-Catenin can suppress the activity of Arp2/3 by competing for actin filaments. These findings lead to a model for adherens junction formation in which clustering of the cadherin–β-catenin complex recruits high levels of α-catenin that can suppress the Arp2/3 complex, leading to cessation of lamellipodial movement and formation of a stable contact. Thus α-catenin appears to play a central role in cell–cell contact formation.