Gem associates with ezrin and acts via the Rho-GAP protein gmip to down-regulate the Rho pathway
Gem associates with ezrin and acts via the Rho-GAP protein gmip to down-regulate the Rho pathway
复制标题
DOI：
10.1091/mbc.e06-06-0510
复制
发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
de Gunzburg, Jean
中科院分区：
文献类型：
--
作者：
Hatzoglou, Anastassia;Ader, Isabelle;de Gunzburg, Jean
Gem是Ras超家族的一种蛋白，在调节电压门控Ca 2+通道和细胞骨架重组中起作用。我们现在报告说，GTP结合的宝石相互作用的膜细胞骨架连接蛋白Ezrin在其活跃的状态下，和宝石结合到活跃的Ezrin在细胞中。Gem和Ezrin的共表达诱导细胞伸长，伴随着肌动蛋白应力纤维的消失和大多数粘着斑的塌陷。当用血清刺激单独表达Gem的细胞并需要表达ERM蛋白时，引起相同的形态学效应。我们发现，内源性宝石下调活性RhoA和肌动蛋白应力纤维的水平。Gem在Rho下游的影响，即，ERM磷酸化以及肌动蛋白应力纤维和大多数粘着斑的消失需要Gem的Rho-GAP伴侣Gmip，Gmip是一种在Gem诱导细胞伸长的条件下在膜中富集的蛋白质。我们的研究结果表明，宝石结合活性埃兹蛋白在质膜-细胞骨架界面，并通过Rho-GAP蛋白Gmip下调依赖于Rho通路的过程。
Gem is a protein of the Ras superfamily that plays a role in regulating voltage-gated Ca2+ channels and cytoskeletal reorganization. We now report that GTP-bound Gem interacts with the membrane-cytoskeleton linker protein Ezrin in its active state, and that Gem binds to active Ezrin in cells. The coexpression of Gem and Ezrin induces cell elongation accompanied by the disappearance of actin stress fibers and collapse of most focal adhesions. The same morphological effect is elicited when cells expressing Gem alone are stimulated with serum and requires the expression of ERM proteins. We show that endogenous Gem down-regulates the level of active RhoA and actin stress fibers. The effects of Gem downstream of Rho, i.e., ERM phosphorylation as well as disappearance of actin stress fibers and most focal adhesions, require the Rho-GAP partner of Gem, Gmip, a protein that is enriched in membranes under conditions in which Gem induced cell elongation. Our results suggest that Gem binds active Ezrin at the plasma membrane-cytoskeleton interface and acts via the Rho-GAP protein Gmip to down-regulate the processes dependent on the Rho pathway.