TY - JOUR T1 - Mechanism of the cadherin-catenin F-actin catch bond interaction JF - bioRxiv DO - 10.1101/2022.05.06.490842 SP - 2022.05.06.490842 AU - Amy Wang AU - Alexander R. Dunn AU - William I. Weis Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/05/06/2022.05.06.490842.abstract N2 - Mechanotransduction at cell-cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At cell-cell junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense and transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, is weak in solution but is strengthened by applied force due to force-dependent transitions between weak and strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that the catch bond property principally resides in the αE-catenin actin-binding domain (ABD). Consistent with our previously proposed model, deletion of the first helix of the five-helix ABD bundle enables stable interactions with F-actin under minimal load that are well-described by a single-state slip bond, even when αE-catenin is complexed with β-catenin and E-cadherin. Our data argue for a conserved catch bond mechanism for adhesion proteins with structurally similar ABDs. We also demonstrate that a stably bound ABD strengthens load-dependent binding interactions between a neighboring complex and F-actin, but the presence of the other αE-catenin domains weakens this effect. These results provide mechanistic insight to the cooperative binding of the cadherin-catenin complex to F-actin, which regulate dynamic cytoskeletal linkages in epithelial tissues.Competing Interest StatementThe authors have declared no competing interest. ER -