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An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns

机译:兴奋性Rho GTPase信号网络产生动态的亚细胞收缩模式

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摘要

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator–inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits itself by local recruitment of actomyosin and the associated RhoGAP Myo9b. This network structure enables spontaneous, self-limiting patterns of subcellular contractility that can explore mechanical cues in the extracellular environment. Indeed, actomyosin pulse frequency in cells is altered by matrix elasticity, showing that coupling of contractility pulses to environmental deformations modulates network dynamics. Thus, our study reveals a mechanism that integrates intracellular biochemical and extracellular mechanical signals into subcellular activity patterns to control cellular contractility dynamics.
机译:基于Rho GTPase的信号网络通过协调时空的突出和收缩来控制细胞动力学。在这里,我们揭示了一个产生脉冲并传播细胞收缩波的信号网络。这些动态模式是通过激活剂-抑制剂网络的自组织而出现的,其中小型GTPase Rho通过募集其激活剂鸟嘌呤核苷酸交换因子GEF-H1来增强其活性。 Rho还通过放生肌动球蛋白和相关的RhoGAP Myo9b来抑制自身。这种网络结构实现了亚细胞收缩的自发性,自限性模式,可以探索细胞外环境中的机械信号。确实,细胞中的肌动球蛋白脉冲频率通过基质弹性改变,表明收缩性脉冲与环境变形的耦合调节了网络动力学。因此,我们的研究揭示了一种将细胞内生化和细胞外机械信号整合到亚细胞活动模式中以控制细胞收缩动态的机制。

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