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

从酵母到人类的真核生物中存在小的G蛋白，构成了一个由一百多名成员组成的超家族。该超家族在结构上至少分为五个家庭：RAS，RHO，RAB，SARL/ARF和RAN家庭。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家族调节蔬菜贩运；跑步的家族调节核眼质运输。已经分离出许多小G蛋白的上游调节剂和下游效应。在本研究项目中，我们研究了小G蛋白，尤其是RAB和RHO家族的激活和作用模式。1。 RAB家族的调节机制：Rab3a是Rab家族的成员，它特别涉及神经递质从神经末端释放。我们已经隔离了其调节蛋白，称为Rab GDI，Rab3…更多GEP和RAB3 GAP。在该研究项目中，我们表明这些蛋白质通过调节RAB3A.2调节神经递质释放过程。 Rab家族的下游途径：我们隔离了Rab3a的效应子，名为Rabphilin-3a。在该研究项目中，我们已经表明，Rabphilin-3a实际上使用鱿鱼巨型轴突系统在神经递质释放中起着至关重要的作用。此外，我们已经确定了一个名为Rabphilin-11的Rab11的效应因子，发现Rab11-Rabphilin-11系统通过调节囊泡回收来参与细胞迁移。3。 Rho家族的调节机制：我们发现了一种新型的GDP/GTP交换蛋白Cdc42，名为Frabin，并表明Frabin-CDC42途径是细胞迁移的最上游调节剂。4。 Rho家族的下游途径：在酿酒酵母中，我们分离了RHO，BNI1和BNR1的两个下游效应，并证明Rho通过这些靶标调节肌动蛋白细胞骨骼和微管，从而导致萌芽或细胞动力学。在哺乳动物细胞中，岩石，一种丝氨酸/苏氨酸蛋白激酶和BNI1的哺乳动物对应物MDIA协同调节肌动蛋白细胞骨架的重组。我们还表明，RAC和CDC42调节基于钙粘蛋白的细胞粘附。较少的