Allosteric regulation of cell adhesion machinery under tension

Our study aims to understand how α-catenin functions as a mechanosensitive F-actin-binding protein to control the cadherin-actin linkage crucial for cadherin-mediated cell-cell adhesion. We determined crystal structures of the dimeric α-catenin actin-binding domain (ABD) with an enhanced F-actin binding mutation, and discovered that an N-terminal α1-helix plays a key role in the binding and bundling of F-actin. Remarkably, our biochemical and cell biology data unveiled the involvement of α1-helix in the mechanosensory function of α-catenin during dynamic adherens junction (AJ) remodelling in cellulo and in vivo. Based on these results, we propose a new model of force-dependent interactions between cadherin-catenin complexes and the actin cytoskeleton facilitated by α-catenin at AJs.