Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance
Arp2/3-Branched Actin Maintains an Active Pool of GTP-RhoA and Controls RhoA Abundance
复制标题
Arp2/3 分支肌动蛋白维持 GTP-RhoA 的活跃池并控制 RhoA 丰度
DOI：
10.3390/cells8101264
复制
发表时间：
2019-10-01
期刊：
影响因子：
6
通讯作者：
Wu, Congying
中科院分区：
文献类型：
--
作者：
Huang, Yuxing;Yi, Xin;Wu, Congying
小GTP酶在精确的时空控制下调节细胞骨架动力学、细胞运动和分裂。不同的小GTP酶表现出串扰，以发挥反馈反应或在信号转导过程中协同作用。然而，特定的细胞骨架成分是否以及如何反馈到上游信号传导因子仍然很难理解。在这里，我们报告了一个有趣的发现，破坏Arp 2/3分支肌动蛋白特异性降低RhoA活性，但上调其总蛋白丰度。我们进一步剖析了这些情况下的机制，并确定了改变cornein/p190 RhoGAP相互作用和减弱CCM 2/Smurf 1结合参与GTP-RhoA减少和总RhoA增加，分别。此外，我们发现Arp 2/3抑制诱导的胞质分裂缺陷可以通过激活RhoA来挽救。我们的研究揭示了一个复杂的反馈从肌动蛋白细胞骨架的小GTdR。我们的工作突出了Arp 2/3分支的肌动蛋白在信号转导中的作用，除了其功能，作为关键的细胞骨架成分，以维持细胞的形态和运动。
Small GTPases regulate cytoskeletal dynamics, cell motility, and division under precise spatiotemporal control. Different small GTPases exhibit cross talks to exert feedback response or to act in concert during signal transduction. However, whether and how specific cytoskeletal components’ feedback to upstream signaling factors remains largely elusive. Here, we report an intriguing finding that disruption of the Arp2/3-branched actin specifically reduces RhoA activity but upregulates its total protein abundance. We further dissect the mechanisms underlying these circumstances and identify the altered cortactin/p190RhoGAP interaction and weakened CCM2/Smurf1 binding to be involved in GTP-RhoA reduction and total RhoA increase, respectively. Moreover, we find that cytokinesis defects induced by Arp2/3 inhibition can be rescued by activating RhoA. Our study reveals an intricate feedback from the actin cytoskeleton to the small GTPase. Our work highlights the role of Arp2/3-branched actin in signal transduction aside from its function in serving as critical cytoskeletal components to maintain cell morphology and motility.