Mechanical Roles of Vinculin/β-catenin interaction in Adherens Junction

Summary Mechanical force transmission through the adherens junctions (AJs) are highly regulated processes essential for multicellular organization of tissues. AJ proteins such as E-cadherin, α-catenin, and vinculin have been shown to be sensing or bearing mechanical forces being transmitted between the actin cytoskeleton and the intercellular contacts. However, the molecular organization and connectivity of these components remains not well understood. Using a super-resolution microscopy approach, we report that vinculin, once activated, could form a direct structural connection with β-catenin, which can bypass α-catenin, one of the main mechanotransducers in AJs. Direct vinculin/β-catenin interaction is capable of supporting mechanical tension and contributes to the stabilization of the cadherin-catenin complexes. These findings suggest a multi-step model for the force-dependent reinforcement of AJs whereby α-catenin may serve as the initial catalytic activator of vinculin, followed by vinculin translocation to form a direct link between E-cadherin-bound β-catenin and the actin cytoskeleton.