Neighborly relations: cadherins and mechanotransduction

Abstract

Cell-cell adhesions are sites where cells experience and resist tugging forces. It has long been postulated, but not directly tested, that cadherin adhesion molecules may serve in mechanotransduction at cell-cell contacts. In this issue, Le Duc et al. (2010. J. Cell Biol. doi: 10.1083/jcb.201001149) provide direct evidence that E-cadherin participates in a mechanosensing pathway that regulates the actomyosin cytoskeleton to modulate cell stiffness in response to pulling force.

Figure 1.

E-cadherin mechanotransduction. Forces acting on surface E-cadherin molecules activate mechanosensing processes that lead to proportionate mechanical responses from cells. (1) In this model, E-cadherin engaged in homophilic adhesive interactions acts as a surface receptor for forces that tug on cells. (2) This induces an intracellular signaling cascade, which includes events such as alterations in protein conformation (notably α-catenin) and recruitment of proteins such as vinculin. (3 and 4) The subsequent mechanical response involves the actomyosin cytoskeleton (3), which can alter adhesion stiffness (4) by diverse processes such as changes in cortical organization and contractility. One potential outcome is that this cellular response will be felt as a pulling force by the neighboring cell that initiated the cascade, leading to cooperative interactions between the cells.