RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/Actin protrusions in fibroblasts
RhoA-dependent phosphorylation and relocalization of ERM proteins into apical membrane/Actin protrusions in fibroblasts
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DOI：
10.1091/mbc.9.2.403
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发表时间：
1998-02-01
影响因子：
3.3
通讯作者：
Jacks, T
中科院分区：
文献类型：
--
作者：
Shaw, RJ;Henry, M;Jacks, T
ERM蛋白（ezrin，radixin和moesin）是一组带4.1相关的蛋白质，被认为是膜/细胞骨架接头。以前的生物化学研究表明RhoA参与调节ERM蛋白与其膜靶点的结合。然而，这种调节的具体效果和作用机制尚不清楚。我们发现，溶血磷脂酸刺激血清饥饿的NIH 3 T3细胞导致radixin重新定位到顶端膜/肌动蛋白突起，这是由Rho的C3转移酶失活阻断。RhoA的激活等位基因，但不是Pac或CDC 42 Hs，足以诱导顶端膜/肌动蛋白突起和本地化radixin或膜突蛋白到这些结构在Rat 1和NIH 3 T3细胞。溶血磷脂酸处理导致磷酸化的根蛋白再分配到顶端突起。值得注意的是，RhoAV 14或C3转移酶与radixin和膜突蛋白的共转染揭示了RhoA活性对于它们的磷酸化是必要的和足够的。这些发现揭示了RhoA在重组顶端肌动蛋白细胞骨架中的一种新功能，并表明这种功能可能是通过ERM蛋白的磷酸化介导的。
The ERM proteins (ezrin, radixin, and moesin) are a group of band 4.1-related proteins that are proposed to function as membrane/cytoskeletal linkers. Previous biochemical studies have implicated RhoA in regulating the association of ERM proteins with their membrane targets. However, the specific effect and mechanism of action of this regulation is unclear. We show that lysophosphatidic acid stimulation of serum-starved NIH3T3 cells resulted in relocalization of radixin into apical membrane/actin protrusions, which was blocked by inactivation of Rho by C3 transferase. An activated allele of RhoA, but not Pac or CDC42Hs, was sufficient to induce apical membrane/actin protrusions and localize radixin or moesin into these structures in both Rat1 and NIH3T3 cells. Lysophosphatidic acid treatment led to phosphorylation of radixin preceding its redistribution into apical protrusions. Significantly, cotransfection of RhoAV14 or C3 transferase with radixin and moesin revealed that RhoA activity is necessary and sufficient for their phosphorylation. These findings reveal a novel function of RhoA in reorganizing the apical actin cytoskeleton and suggest that this function may be mediated through phosphorylation of ERM proteins.