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Functional interaction between Rho effector proteins

Rho 效应蛋白之间的功能相互作用

基本信息

批准号：
18590262
负责人：
ISHIZAKI Toshimasa
金额：
$ 2.5万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590262/
关键词：
Rho actin cytoskeleton mDia ROCK cytokinesis cell migration vasculogenesis 細胞接着胚発生

项目摘要

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. We found that 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 in rat C6 glioma cells.mDia proteins belong to the formin family proteins that catalyze actin nucleation and polymerization. Although formin family proteins of nonmammalian species such as Drosophila diaphanous are essential in cytokinesis, whether and how mDia proteins function in cytokinesis rema … More in unknown. To address this issue, we depleted each of the three mDia isoforms in NIH 3T3 cells by RNA interference. Depletion of mDia2 selectively increased the number of binucleate cells. mDia2 accumulates in the cleavage furrow during anaphase to telophase, and concentrates in the midbody at the end of cytokinesis. Depletion of mDia2 induced contraction at aberrant sites of dividing cells, where contractile ring components such as RhoA, myosin, anillin, and phosphorylated ERM accumulated. Treatment with blebbistatin suppressed abnormal contraction, corrected localization of the above components, and revealed that the amount of F-actin at the equatorial region during anaphase/telophase was significantly decreased with mDia2 RNAi. These results demonstrate that mDia2 is essential in mammalian cell cytokinesis and that mDia2-induced F-actin forms a scaffold for the contractile ring and maintains its position in the middle of a dividing cell.Furthermore, we are also analyzing the role of another Rho effector molecule, ROCK, in vasculogenesis during embryonic development. Less

定向细胞迁移需要细胞极化和粘附周转，其中肌动蛋白细胞骨架和微管起关键作用。Rho GTP酶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，Cdc 42调节细胞极性，Rac起膜突出作用。然而，Rho在迁移中的作用鲜为人知。Rho作用于两个主要效应子ROCK和mDia 1，其中mDia 1产生直的肌动蛋白丝并排列微管。我们发现Rho-mDia 1通路通过排列微管和肌动蛋白丝并将Apc/Cdc 42和c-Src递送到大鼠C6胶质瘤细胞中各自的作用位点来调节极化和粘附周转。虽然mDia家族蛋白在非哺乳动物如果蝇的胞质分裂中是必需的，但mDia蛋白在胞质分裂中是否以及如何发挥作用仍有待进一步研究。 ...更多信息在未知的。为了解决这个问题，我们通过RNA干扰耗尽NIH 3 T3细胞中的三种mDia同种型中的每一种。消耗mDia 2选择性地增加双核细胞的数量。mDia 2在分裂后期积累在卵裂沟中，并在胞质分裂末期集中在中间体中。消耗mDia 2诱导收缩异常网站的分裂细胞，收缩环组件，如RhoA，肌球蛋白，苯胺，和磷酸化的ERM积累。用blebbistatin治疗抑制异常收缩，纠正上述组分的定位，并显示在后期/末期期间赤道区的F-肌动蛋白的量用mDia 2 RNAi显著降低。这些结果表明，mDia 2是必不可少的哺乳动物细胞的胞质分裂和mDia 2诱导的F-肌动蛋白形成的收缩环的支架，并保持其在分裂cell. Further的中间位置，我们还分析了另一个Rho效应分子，ROCK，在胚胎发育过程中的血管发生的作用。少