α-Catenin contributes to the strength of E-cadherin–p120 interactions

Cadherin–catenin interactions play an important role in cadherin-mediated adhesion. Here we present strong evidence that in the cadherin–catenin complex α-catenin contributes to the binding strength of another catenin, p120, to the same complex. Specifically, we found that a β-catenin–uncoupled cadherin mutant interacts much more weakly with p120 than its full-size counterpart and that it is rapidly endocytosed from the surface of A-431 cells. We also showed that p120 overexpression stabilizes this mutant on the cell surface. Examination of the α-catenin–deficient MDA-MB-468 cells and their derivates in which α-catenin was reintroduced showed that α-catenin reinforces E-cadherin–p120 association. Finally, a cross-linking analysis of the cadherin–catenin complex indicated that a large loop located in the middle of the p120 arm-repeat domain is in close spatial vicinity to the amino-terminal VH1 domain of α-catenin. The six amino acid–long extension of this loop, caused by an alternative splicing, weakens p120 binding to cadherin. The data suggest that α-catenin–p120 contact within the cadherin–catenin complex can regulate cadherin trafficking.