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Modes of activation and action of Small G proteins

小 G 蛋白的激活和作用模式

基本信息

批准号：
10044285
负责人：
TAKAI Yoshimi
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044285/
关键词：
Small G Protein Rho Rab Rab3A Rabphilin-3A Rabphilin-11 BNI1 Frabin BNT1 RabGD1 SHP-2 SPA2 mDia ROCK

项目摘要

Small G proteins exist in eukaryotes from yeast to human and constitute a superfamily consisting of more than one hundred members. This superfamily is structurally classified into at least five families : the Ras, Rho, Rab, Sarl/Arf, and Ran families. They regulate a wide variety of cell functions : The Ras family regulates gene expression; the Rho family regulates reorganization of cytoskeleton and gene expression; the Rab and Sarl/Arf families regulate vesicle trafficking; and the Ran family regulates nucleocytoplasmic transport. Many upstream regulators and downstream effectors of small G proteins have been isolated. In the present research project, we have studied the modes of activation and action of small G proteins, especially the Rab and Rho families.1. The regulatory mechanism of the Rab family : Rab3A is a member of the Rab family which is particularly implicated in neurotransmitter release from the nerve terminal. We had isolated its regulatory proteins, named Rab GDI, Rab3 … More GEP, and Rab3 GAP. In this research project, we have shown that these proteins modulate the neurotransmitter release process through regulation of Rab3A.2. The downstream pathway of the Rab family : We had isolated an effector of Rab3A, named Rabphilin-3A. In this research project, we have shown that Rabphilin-3A actually plays a crucial role in neurotransmitter release using the squid giant axon system. Moreover, we have identified an effector of Rab11, named Rabphilin-11, and found that the Rab11-Rabphilin-11 system is involved in cell migration through regulation of the vesicle recycling.3. The regulatory mechanism of the Rho family : We have discovered a novel GDP/GTP exchange protein of Cdc42, named Frabin, and shown that the Frabin-Cdc42 pathway functions as the most upstream regulator for cell migration.4. The downstream pathway of the Rho family : In S. cerevisiae, we have isolated two downstream effectors of Rho, BNI1 and BNR1, and demonstrated that Rho regulates actin cytoskeleton and microtubules through these targets, leading to budding or cytokinesis. In mammalian cells, ROCK, a serine/threonine protein kinase, and mDia, a mammalian counterpart of BNI1, cooperatively regulate reorganization of the actin cytoskeleton. We have also shown that Rac and Cdc42 regulate cadherin-based cell-cell adhesion. Less

小G蛋白存在于从酵母到人类的真核生物中，构成了一个由一百多个成员组成的超家族。该超家族在结构上分为至少五个家族：Ras、Rho、Rab、Sarl/Arf和Ran家族。它们调节多种细胞功能：Ras家族调节基因表达; Rho家族调节细胞骨架和基因表达的重组; Rab和Sarl/Arf家族调节囊泡运输; Ran家族调节核质运输。已经分离出许多小G蛋白的上游调节子和下游效应子。在本研究项目中，我们研究了小G蛋白的激活和作用模式，特别是Rab和Rho家族。Rab家族的调节机制：Rab 3A是Rab家族的成员，特别涉及神经末梢的神经递质释放。我们分离了其调控蛋白，命名为RabGDI、Rab 3 ...更多信息 GEP和Rab 3 GAP。在这个研究项目中，我们已经证明这些蛋白质通过调节Rab3A.2来调节神经递质的释放过程。Rab家族的下游通路：我们分离了Rab 3A的效应子，命名为Rabphilin-3A。在这个研究项目中，我们已经证明Rabphilin-3A实际上在鱿鱼巨轴突系统的神经递质释放中起着至关重要的作用。此外，我们还鉴定了Rab 11的一种效应物Rabphilin-11，发现Rab 11-Rabphilin-11系统通过调节囊泡的回收参与细胞迁移. Rho家族的调控机制：我们发现了Cdc 42的一个新的GDP/GTP交换蛋白，命名为Frabin，并表明Frabin-Cdc 42通路是细胞迁移的最上游调控因子. Rho家族的下游通路：在S.在酿酒酵母中，我们分离了Rho的两个下游效应子BNI 1和BNR 1，并证明Rho通过这些靶点调节肌动蛋白细胞骨架和微管，导致出芽或胞质分裂。在哺乳动物细胞中，ROCK（丝氨酸/苏氨酸蛋白激酶）和mDia（BNI 1的哺乳动物对应物）协同调节肌动蛋白细胞骨架的重组。我们还发现Rac和Cdc 42调节基于钙粘蛋白的细胞间粘附。少