Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens

Abstract

The biological impact of Rho depends critically on the precise subcellular localization of its active, GTP-loaded form. The spatio-temporal balance between molecules that promote nucleotide exchange or GTP hydrolysis can potentially determine the sites of Rho signalling. But how these activities may be coordinated is poorly understood. We now report a molecular pathway that achieves exactly this coordination at the epithelial zonula adherens. We identify an extramitotic activity of the centralspindlin complex, better understood as a cytokinetic regulator, which localises to the zonula adherens during interphase by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the Rho GEF, Ect2, to the zonula adherens to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localisation of p190RhoGAP B, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is utilized in interphase cells to control the Rho GTPase cycle at the zonula adherens.