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首页> 外文期刊>Molecular and Cellular Biology >The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-Src
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The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-Src

机译:Rho-mDia1通路通过动员Apc和c-Src调节迁移细胞中的细胞极性和粘着斑转变。

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Directed cell migration requires cell polarization and adhesion turnover, in which the actin cytoskeleton and microtubules work critically. The Rho GTPases induce specific types of actin cytoskeleton and regulate microtubule dynamics. In migrating cells, Cdc42 regulates cell polarity and Rac works in membrane protrusion. However, the role of Rho in migration is little known. Rho acts on two major effectors, ROCK and mDia1, among which mDia1 produces straight actin filaments and aligns microtubules. Here we depleted mDia1 by RNA interference and found that mDia1 depletion impaired directed migration of rat C6 glioma cells by inhibiting both cell polarization and adhesion turnover. Apc and active Cdc42, which work together for cell polarization, localized in the front of migrating cells, while active c-Src, which regulates adhesion turnover, localized in focal adhesions. mDia1 depletion impaired localization of these molecules at their respective sites. Conversely, expression of active mDia1 facilitated microtubule-dependent accumulation of Apc and active Cdc42 in the polar ends of the cells and actin-dependent recruitment of c-Src in adhesions. Thus, the Rho-mDia1 pathway regulates polarization and adhesion turnover by aligning microtubules and actin filaments and delivering Apc/Cdc42 and c-Src to their respective sites of action.
机译:定向细胞迁移需要细胞极化和粘附转换,其中肌动蛋白的细胞骨架和微管至关重要。 Rho GTPases诱导特定类型的肌动蛋白细胞骨架并调节微管动力学。在迁移细胞中,Cdc42调节细胞极性,而Rac在膜突出中起作用。但是,Rho在迁移中的作用鲜为人知。 Rho作用在ROCK和mDia1这两个主要效应子上,其中mDia1产生直的肌动蛋白丝并排列微管。在这里,我们通过RNA干扰消除了mDia1,并发现mDia1耗尽通过抑制细胞极化和黏附更新而损害了大鼠C6胶质瘤细胞的定向迁移。 Apc和活性Cdc42共同作用于细胞极化,位于迁移细胞的前部,而活性c-Src调节粘着力转换,作用于粘着斑。 mDia1耗尽削弱了这些分子在其各自部位的定位。相反,活性mDia1的表达促进了细胞极性末端中Apc和活性Cdc42的微管依赖性积累,并促进了粘附性中c-Src的肌动蛋白依赖性募集。因此,Rho-mDia1途径通过对齐微管和肌动蛋白丝并将Apc / Cdc42和c-Src传递到它们各自的作用部位来调节极化和粘附转换。

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