RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.
RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6.
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DOI：
10.1016/j.devcel.2017.04.010
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发表时间：
2017-05-08
影响因子：
11.8
通讯作者：
Way M
中科院分区：
文献类型：
--
作者：
Durkin CH;Leite F;Cordeiro JV;Handa Y;Arakawa Y;Valderrama F;Way M
RhoA介导的肌动蛋白皮质中肌球蛋白-II活性的调节控制细胞在各种细胞过程（包括细胞迁移和分裂）中收缩和起泡的能力。细胞收缩和起泡也经常发生，作为许多不同病毒感染期间观察到的细胞病变效应的一部分。我们现在证明，牛痘病毒蛋白F11，它定位于质膜，需要从感染后2小时ROCK介导的细胞收缩。奇怪的是，F11诱导的细胞收缩依赖于RhoC而不是RhoA向ROCK的信号传导。此外，RhoC驱动的细胞收缩依赖于F11对RhoD信号传导的上游抑制。这种抑制阻止RhoD调节其下游效应子Pak 6，从而减轻激酶对RhoC的抑制。我们对牛痘的观察现在已经证明，RhoD将Pak 6募集到质膜上，以拮抗细胞收缩和起泡期间的RhoC信号传导。牛痘F11蛋白是病毒诱导的细胞收缩和起泡所必需的F11诱导的细胞收缩依赖于RhoC，而不是RhoA，信号传导到ROCK RhoD招募Pak 6到质膜以拮抗RhoC信号传导F11抑制RhoD信号传导到其下游效应物Pak 6许多不同的病毒感染诱导细胞收缩和起泡。Durkin，Leite，et al.显示在牛痘感染期间，RhoC而不是RhoA调节这种ROCK介导的细胞收缩的细胞病变效应。他们描绘了RhoC调节的途径，其中病毒蛋白F11通过RhoD募集的Pak 6阻断RhoC拮抗作用。
RhoA-mediated regulation of myosin-II activity in the actin cortex controls the ability of cells to contract and bleb during a variety of cellular processes, including cell migration and division. Cell contraction and blebbing also frequently occur as part of the cytopathic effect seen during many different viral infections. We now demonstrate that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from 2 hr post infection. Curiously, F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. This inhibition prevents RhoD from regulating its downstream effector Pak6, alleviating the suppression of RhoC by the kinase. Our observations with vaccinia have now demonstrated that RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling during cell contraction and blebbing. Vaccinia F11 protein is required for virus-induced cell contraction and blebbing F11-induced cell contraction depends on RhoC, but not RhoA, signaling to ROCK RhoD recruits Pak6 to the plasma membrane to antagonize RhoC signaling F11 inhibits RhoD signaling to its downstream effector Pak6 Many different viral infections induce cell contraction and blebbing. Durkin, Leite, et al. show that during vaccinia infection, RhoC and not RhoA regulates this ROCK-mediated cytopathic effect of cell contraction. They delineate a pathway for RhoC regulation, in which the viral protein F11 blocks RhoC antagonism by RhoD-recruited Pak6.