β-catenin condensation facilitates clustering of the cadherin/catenin complex and formation of nascent cell-cell junctions

Abstract

Cadherin-based junctions establish dynamically regulated adhesion between cells to coordinate tissue integrity and morphogenetic movements. Adhesion strength can be modulated by the organization of individual cadherin complexes into lateral clusters. Here, we identify a clustering mechanism of the cadherin complex established by its core component β-catenin. We show that the disordered termini of β-catenin drive the formation of condensates that incorporate other components of the cadherin complex in vitro. Using β-catenin mutants with hampered condensation, we demonstrate that β-catenin condensation nucleates the formation of submicron cadherin/catenin clusters that further develop into stable sites of adhesion. Furthermore, we show that β-catenin-dependent clustering ensures the efficient formation of de novo cell-cell adhesions. Our data thus indicate a role for β-catenin condensates in the supramolecular organization of the cadherin complex, and reveal that the function of β-catenin in the cadherin complex extends beyond connecting cadherin to α-catenin and the actin cytoskeleton.