beta-catenin condensation facilitates clustering of the cadherin/catenin complex and formation of nascent cell-cell junctions #MMPMID41353217
Monster JL; Manzato C; van der Beek JA; Pannekoek WJ; Hummelink JA; Hadders MA; de Heus C; Klumperman J; Schuijers J; Gloerich M
Nat Commun 2025[Dec]; ? (?): ? PMID41353217show ga
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 beta-catenin. We show that the disordered termini of beta-catenin drive the formation of condensates that incorporate other components of the cadherin complex in vitro. Using beta-catenin mutants with hampered condensation, we demonstrate that beta-catenin condensation nucleates the formation of submicron cadherin/catenin clusters that further develop into stable sites of adhesion. Furthermore, we show that beta-catenin-dependent clustering ensures the efficient formation of de novo cell-cell adhesions. Our data thus indicate a role for beta-catenin condensates in the supramolecular organization of the cadherin complex, and reveal that the function of beta-catenin in the cadherin complex extends beyond connecting cadherin to alpha-catenin and the actin cytoskeleton.