Vinculin, cadherin mechanotransduction and homeostasis of cell–cell junctions

Cell adhesion junctions characteristically arise from the cooperative integration of adhesion receptors, cell signalling pathways and the cytoskeleton. This is exemplified by cell–cell interactions mediated by classical cadherin adhesion receptors. These junctions are sites where cadherin adhesion systems functionally couple to the dynamic actin cytoskeleton, a process that entails physical interactions with many actin regulators and regulation by cell signalling pathways. Such integration implies a potential role for molecules that may stand at the interface between adhesion, signalling and the cytoskeleton. One such candidate is the cortical scaffolding protein, vinculin, which is a component of both cell–cell and cell–matrix adhesions. While its contribution to integrin-based adhesions has been extensively studied, less is known about how vinculin contributes to cell–cell adhesions. A major recent advance has come with the realisation that cadherin adhesions are active mechanical structures, where cadherin serves as part of a mechanotransduction pathway by which junctions sense and elicit cellular responses to mechanical stimuli. Vinculin has emerged as an important element in cadherin mechanotransduction, a perspective that illuminates its role in cell–cell interactions. We now review its role as a cortical scaffold and its role in cadherin mechanotransduction.