Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis

Terry, Stephen J., Zihni, Ceniz, Elbediwy, Ahmed, Vitiello, Elisa, Leefa Chong San, Isabelle V., Balda, Maria S. and Matter, Karl (2011) Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nature Cell Biology, 13(2), pp. 159-166. ISSN (print) 1465-7392

Full text not available from this archive.

Abstract

Signalling by the GTPase RhoA, a key regulator of epithelial cell behaviour, can stimulate opposing processes: RhoA can promote junction formation and apical constriction, and reduce adhesion and cell spreading. Molecular mechanisms are thus required that ensure spatially restricted and process-specific RhoA activation. For many fundamental processes, including assembly of the epithelial junctional complex, such mechanisms are still unknown. Here we show that p114RhoGEF is a junction-associated protein that drives RhoA signalling at the junctional complex and regulates tight-junction assembly and epithelial morphogenesis. p114RhoGEF is required for RhoA activation at cell-cell junctions, and its depletion stimulates non-junctional Rho signalling and induction of myosin phosphorylation along the basal domain. Depletion of GEF-H1, a RhoA activator inhibited by junctional recruitment, does not reduce junction-associated RhoA activation. p114RhoGEF associates with a complex containing myosin II, Rock II and the junctional adaptor cingulin, indicating that p114RhoGEF is a component of a junction-associated Rho signalling module that drives spatially restricted activation of RhoA to regulate junction formation and epithelial morphogenesis.

Item Type: Article
Additional Information: This research was supported by Fight for Sight and the Wellcome Trust.
Research Area: Biological sciences
Cancer studies
Faculty, School or Research Centre: Faculty of Science (until 2011) > School of Life Sciences
Faculty of Science (until 2011) > School of Pharmacy and Chemistry
Depositing User: Ahmed Elbediwy
Date Deposited: 11 Feb 2019 16:25
Last Modified: 11 Feb 2019 16:25
DOI: https://doi.org/10.1038/ncb2156
URI: http://eprints.kingston.ac.uk/id/eprint/42628

Actions (Repository Editors)

Item Control Page Item Control Page