Tyrosine dephosphorylated cortactin downregulates contractility at the epithelial zonula adherens through SRGAP1.

ABSTRACT: Contractile adherens junctions support cell-cell adhesion, epithelial integrity, and morphogenesis. Much effort has been devoted to understanding how contractility is established; however, less is known about whether contractility can be actively downregulated at junctions nor what function this might serve. We now identify such an inhibitory pathway that is mediated by the cytoskeletal scaffold, cortactin. Mutations of cortactin that prevent its tyrosine phosphorylation downregulate RhoA signaling and compromise the ability of epithelial cells to generate a contractile zonula adherens. This is mediated by the RhoA antagonist, SRGAP1. We further demonstrate that this mechanism is co-opted by hepatocyte growth factor to promote junctional relaxation and motility in epithelial collectives. T

SUBMITTER: Liang X 

PROVIDER: S-EPMC5629210 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature