Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions
Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions
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DOI：
10.1038/ncb3239
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发表时间：
2015-10-01
影响因子：
21.3
通讯作者：
Yap, Alpha S.
中科院分区：
文献类型：
--
作者：
Priya, Rashmi;Gomez, Guillermo A.;Yap, Alpha S.
在上皮小带粘附（ZA）上的肌动球蛋白产生组织完整性和形态发生的连接张力。这需要RhoA GTPase，它在ZA上建立了一个非常稳定的活性区域。因此，必须存在机制，以在群体水平上赋予连接RhoA信号的稳健性。我们现在确定了一个反馈网络，它可以从动态元素中产生稳定的介观RhoA区。关键是通过肌凝蛋白II将ROCK1支架到ZA。ROCK1通过磷酸化Rnd3来阻止Rho抑制因子p190B RhoGAP在皮层的募集，从而保护连接RhoA。结合预测模型和实验，我们证明了该网络构成了一个双稳态的动力系统，该系统在ZA的种群水平上实现。因此，RhoA区的稳定性是肌凝蛋白II向RhoA反馈的相互作用网络的一个紧急结果。
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.