Functional domains of α-catenin required for the strong state of cadherin-based cell adhesion

Abstract

The interaction of cadherin-catenin complex with the actin-based cytoskeleton through α-catenin is indispensable for cadherin-based cell adhesion activity. We reported previously that E-cadherin-α-catenin fusion molecules showed cell adhesion and cytoskeleton binding activities when expressed in nonepithelial L cells. Here, we constructed deletion mutants of E-cadherin-α-catenin fusion molecules lacking various domains of α-catenin and introduced them into L cells. Detailed analysis identified three distinct functional domains of α-catenin: a vinculin/α-actinin-binding domain, a ZO- 1-binding domain, and an adhesion-modulation domain. Furthermore, cell dissociation assay revealed that the fusion molecules containing the ZO-1- binding domain in addition to the adhesion-modulation domain conferred the strong state of cell adhesion activity on transfectants, although those lacking the ZO-1-binding domain conferred only the weak state. The disorganization of actin-based cytoskeleton by cytochalasin D treatment shifted the cadherin-based cell adhesion from the strong to the weak state. In the epithelial cells, where α-catenin was not precisely colocalized with ZO-1, the ZO-1-binding domain did not completely support the strong state of cell adhesion activity. Our studies showed that the interaction of α- catenin with the actin-based cytoskeleton through the ZO-1-binding domain is required for the strong state of E-cadherin-based cell adhesion activity.