Journal
NATURE CELL BIOLOGY
Volume 17, Issue 10, Pages 1282-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3239
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Funding
- National Health and Medical Research Council of Australia [1044041, 1037320, 1067405]
- Kids Cancer Project of the Oncology Research Foundation
- EMPathy National Collaborative Research Program of the National Breast Cancer Foundation (Australia) [CG-10-04]
- University of Queensland Early Career Research Grant [2012003354]
- ANZ Trustees PhD Scholarship in Medical Research
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Actomyosin at the epithelial zonula adherens (ZA) generates junctional tension for tissue integrity and morphogenesis. This requires the RhoA GTPase, which establishes a strikingly stable active zone at the ZA. Mechanisms must then exist to confer robustness on junctional RhoA signalling at the population level. We now identify a feedback network that generates a stable mesoscopic RhoA zone out of dynamic elements. The key is scaffolding of ROCK1 to the ZA by myosin II. ROCK1 protects junctional RhoA by phosphorylating Rnd3 to prevent the cortical recruitment of the Rho suppressor, p190B RhoGAP. Combining predictive modelling and experimentation, we show that this network constitutes a bistable dynamical system that is realized at the population level of the ZA. Thus, stability of the RhoA zone is an emergent consequence of the network of interactions that allow myosin II to feedback to RhoA.
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