p116Rip targets myosin phosphatase to the actin cytoskeleton and is essential for RhoA/ROCK-regulated neuritogenesis
p116Rip targets myosin phosphatase to the actin cytoskeleton and is essential for RhoA/ROCK-regulated neuritogenesis
复制标题
DOI：
10.1091/mbc.e04-04-0275
复制
发表时间：
2004-12-01
影响因子：
3.3
通讯作者：
Moolenaar, WH
中科院分区：
文献类型：
--
作者：
Mulder, J;Ariaens, A;Moolenaar, WH
RhoA-Rho激酶（ROCK）通路的激活在许多细胞系统中刺激肌动球蛋白驱动的收缩性，主要是通过ROCK介导的肌球蛋白II轻链磷酸酶抑制。在神经元细胞中，RhoA-ROCK-肌动球蛋白途径发出细胞变圆、生长锥塌陷和神经突收缩的信号;相反，RhoA/ROCK的抑制促进细胞伸展和神经突生长。肌动蛋白结合蛋白p116（Rip）的N-末端区域束F-肌动蛋白在体外，有牵连在Rho依赖性神经突起重塑，然而，其功能在很大程度上是未知的。在这里，我们表明，p116（Rip），通过其C-末端卷曲螺旋结构域，直接与肌球蛋白II磷酸酶，MBS 85和MBS 130的肌球蛋白结合调节亚基的C-末端亮氨酸拉链相互作用。RNA干扰诱导的p116 Rip敲低抑制细胞外信号刺激下的细胞伸展和神经突生长，而不干扰肌球蛋白轻链磷酸化的调节。我们的结论是，p116 Rip是必不可少的神经突生长，并可能作为一个支架，以针对肌动蛋白细胞骨架的肌球蛋白磷酸酶复合物。
Activation of the RhoA-Rho kinase (ROCK) pathway stimulates actomyosin-driven contractility in many cell systems, largely through ROCK-mediated inhibition of myosin II light chain phosphatase. In neuronal cells, the RhoA-ROCK-actomyosin pathway signals cell rounding, growth cone collapse, and neurite retraction; conversely, inhibition of RhoA/ROCK promotes cell spreading and neurite outgrowth. The actin-binding protein p116(Rip) whose N-terminal region bundles F-actin in vitro, has been implicated in Rho-dependent neurite remodeling; however, its function is largely unknown. Here, we show that p116(Rip), through its C-terminal coiled-coil domain, interacts directly with the C-terminal leucine zipper of the regulatory myosin-binding subunits of myosin II phosphatase, MBS85 and MBS130. RNA interference-induced knockdown of p116Rip inhibits cell spreading and neurite outgrowth in response to extracellular cues, without interfering with the regulation of myosin light chain phosphorylation. We conclude that p116Rip is essential for neurite outgrowth and may act as a scaffold to target the myosin phosphatase complex to the actin cytoskeleton.