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

Nature Cell Biology volume 14, pages 818–828 (2012)Cite this article

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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.

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Figure 1: The zonula adherens is a microtubule-dependent Rho zone.
Figure 2: ECT2 is a junctional RhoA GEF.
Figure 3: ECT2 is necessary for zonula adherens integrity and junctional tension.
Figure 4: Centralspindlin regulates junctional ECT2–Rho signalling.
Figure 5: α-catenin mediates the junctional retention of ECT2.
Figure 6: α-catenin mediates the junctional retention of centralspindlin.
Figure 7: Centralspindlin inhibits the junctional recruitment of p190B RhoGAP.

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Acknowledgements

We thank our laboratory colleagues for their support and advice, all our colleagues who provided gifts of reagents, and R. Saint who first suggested we think about ECT2. This work was financially supported by the Human Frontiers Science Program, the National Health and Medical Research Council of Australia, Australian Research Council, and the Oncology Children’s Foundation. Confocal microscopy was performed at the IMB/ACRF Cancer Biology Imaging Facility, established with the generous support of the Australian Cancer Research Foundation.

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Author notes

  1. Samantha J. Stehbens

    Present address: Present address: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, California 94143, USA,

  2. Aparna Ratheesh and Guillermo A. Gomez: These authors contributed equally to this work

Authors and Affiliations

  1. Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Brisbane 4072, Australia

    Aparna Ratheesh, Guillermo A. Gomez, Rashmi Priya, Suzie Verma, Eva M. Kovacs, Samantha J. Stehbens & Alpha S. Yap

  2. Cell Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    Kai Jiang & Anna Akhmanova

  3. Gurdon Institute and Department of Physiology, Development and Neuroscience, Cambridge University, Tennis Court Rd, Cambridge CB2 1QN, UK

    Nicholas H. Brown

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Contributions

A.R., S.J.S., A.A. and A.S.Y. conceived the project, A.R., G.A.G., R.P., S.V. and N.H.B. conducted experiments, E.M.K. and K.J. generated reagents, A.R., G.A.G. and A.S.Y. analysed the data and A.R. and A.S.Y. wrote the paper.

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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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