○講演者：Dr. Cristina Bertocchi（Laboratory for Molecular Mechanics of Cell Adhesion- Department of Physiology, Pontificia Universidad Católica de Chile）
○タイトル：Mechanotransduction at cell adhesions
○内容：Cells sense their physical surroundings through molecular nanomachines regulating force transduction and mechanosensing. One of such complexes is the Adherens Junction (AJ), an adhesion complex mediating cell-cell interaction. Within AJ, the protein a-catenin, has been suggested as a force-transducing element. However, it is unlikely that a single dominant tether could bear the load of and regulate such sophisticated and precise system to provide the high morphological plasticity observed in epithelial tissues. Indeed, we have previously unveiled a mechanism by which conformational switch of vinculin (a partner protein of a-catenin) could selectively engage the actin cytoskeleton in response to regulatory mechanochemical signals, effectively functioning as a molecular clutch, to mediate intercellular interactions. This finding implies that the force transduction and regulation at AJ may be more complex than a single tether functioning through a simple on-off model. Using a super-resolution microscopy approach, we report that vinculin, once activated, could form a direct structural connection with b-catenin, which can bypass a-catenin. Direct vinculin/b-catenin interaction can support mechanical tension and contributes to the stabilization of the cadherin-catenin complexes. We thus propose a multi-step mechanochemical process to mediate mechanical connection and the force-dependent molecular mechanics modulating AJ reinforcement in complex biological functions.