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. This can potentially be determined by the balance between molecules that promote nucleotide exchange or GTP hydrolysis. However, 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 localizes to the interphase zonula adherens by interacting with the cadherin-associated protein, α-catenin. Centralspindlin recruits the RhoGEF, ECT2, to activate Rho and support junctional integrity through myosin IIA. Centralspindlin also inhibits the junctional localization of p190 B RhoGAP, which can inactivate Rho. Thus, a conserved molecular ensemble that governs Rho activation during cytokinesis is used in interphase cells to control the Rho GTPase cycle at the zonula adherens. Yap and colleagues identify an extramitotic role for the centralspindlin complex, a Rho signalling regulator during cytokinesis. They show that centralspindlin interacts with α-catenin, and promotes epithelial junctional integrity by recruiting the ECT2 RhoGEF to the zonula adherens, as well as by inhibiting the junctional localization of the p190 B RhoGAP.

Cite this article

Ratheesh, A., Gomez, G., Priya, R. et al. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat Cell Biol 14, 818–828 (2012). https://doi.org/10.1038/ncb2532

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