Cadherin cell–cell adhesion proteins play key roles in tissue morphogenesis and wound healing. Cadherin ectodomains bind in two conformations, X-dimers and strand-swap dimers, with different adhesive properties. However, the mechanisms by which cells regulate ectodomain conformation are unknown. Cadherin intracellular regions associate with several actin-binding proteins including vinculin, which are believed to tune cell–cell adhesion by remodeling the actin cytoskeleton. Here, we show at the single-molecule level, that vinculin association with the cadherin cytoplasmic region allosterically converts weak X-dimers into strong strand-swap dimers and that this process is mediated by myosin II–dependent changes in cytoskeletal tension. We also show that in epithelial cells, ∼70% of apical cadherins exist as strand-swap dimers while the remaining form X-dimers, providing two cadherin pools with different adhesive properties. Our results demonstrate the inside-out regulation of cadherin conformation and establish a mechanistic role for vinculin in this process.

钙粘蛋白细胞 - 细胞粘附蛋白在组织形态发生和伤口愈合中起关键作用。钙粘蛋白胞外域以两种构象结合，即 X-二聚体和链交换二聚体，具有不同的粘合特性。然而，细胞调节胞外域构象的机制尚不清楚。钙粘蛋白细胞内区域与包括纽蛋白在内的几种肌动蛋白结合蛋白相关，据信它们通过重塑肌动蛋白细胞骨架来调节细胞 - 细胞粘附。在这里，我们在单分子水平上表明，与钙粘蛋白细胞质区域的纽蛋白结合变构地将弱 X-二聚体转化为强链交换二聚体，并且该过程由肌球蛋白 II 依赖性细胞骨架张力的变化介导。我们还表明，在上皮细胞中，约 70% 的顶端钙粘蛋白以链交换二聚体的形式存在，而其余的形成 X-二聚体，提供了两个具有不同粘合特性的钙粘蛋白池。我们的研究结果证明了钙粘蛋白构象的由内而外的调节，并在此过程中建立了纽蛋白的机制作用。