β-catenin N- and C-terminal tails modulate the coordinated binding of adherens junction proteins to β-catenin

Abstract

β-Catenin plays a central role in the establishment and regulation of adherens junctions because it interacts with E-cadherin and, through β-catenin, with the actin cytoskeleton β-Catenin is composed of three domains: a central armadillo repeat domain and two N- and C-terminal tails. The C-tail interacts with the armadillo domain and limits its ability to bind E-cadherin and other cofactors. The two β-catenin tails are mutually inter-regulated because the C-tail is also necessary for binding of the N-tail to the armadillo domain. Moreover, the N-tail restricts the interaction of the C-tail with the central domain. Depletion of either of the two tails has consequences for the binding of factors at the other end: deletion of the C-tail increases α-catenin binding, whereas deletion of the N-tail blocks E-cadherin interaction to the armadillo repeats. As an effect of the interconnection of the tails, the association of α-catenin and E-cadherin to β-catenin is interdependent. Thus, binding of α-catenin to the N-tail, through conformational changes that affect the C-tail, facilitates the association of E-cadherin. These results indicate that different cofactors of β-catenin bind coordinately to this protein and indicate how the two terminal ends of β-catenin exquisitely modulate intermolecular binding within junctional complexes.