Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of alpha-catenin, beta-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that beta-catenin can prevent vinculin autoinhibition in the presence of alpha-catenin by occupying vinculin<acute accent>s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where alpha-catenin and beta-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving beta-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking alpha-catenin. Adherens junctions mediate force transmission and connect the cytoskeleton of adjacent cells. This study demonstrates that force transmission can be achieved through direct and functional beta-catenin/vinculin interaction in the absence of alpha-catenin.