Binding between the Junctional Proteins Afadin and PLEKHA7 and Implication in the Formation of Adherens Junction in Epithelial Cells

Adherens junction (AJ) is a specialized cell-cell junction structure that plays a role in mechanically connecting adjacent cells to resist strong contractile forces and to maintain tissue structure, particularly in the epithelium. AJ is mainly comprised of cell adhesion molecules cadherin and nectin and their associating cytoplasmic proteins including beta-catenin, alpha-catenin, p120(ctn), and afadin. Our series of studies have revealed that nectin first forms cell-cell adhesion and then recruits cadherin to form AJ. The recruitment of cadherin by nectin is mediated by the binding of alpha-catenin and p120(ctn) to afadin. Recent studies showed that PLEKHA7 binds to p120(ctn), which is associated with E-cadherin, and maintains the integrity of AJ in epithelial cells. In this study, we showed that PLEKHA7 bound to afadin in addition to p120(ctn) and was recruited to the nectin-3 alpha-based cell-cell adhesion site in a manner dependent on afadin, but not on p120(ctn). The binding of PLEKHA7 to afadin was required for the proper formation of AJ, but not for the formation of tight junction, in EpH4 mousemammarygland epithelial cells. These results indicate that PLEKHA7 plays a cooperative role with nectin and afadin in the proper formation of AJ in epithelial cells.