Function and action of Rab3A in neurotransmitter release

Rab3A 在神经递质释放中的功能和作用

基本信息

批准号：
09670126
负责人：
SHIRATAKI Hiromichi
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670126/
关键词：
small G protein Rab3A neurotransmitter release Tomosyn Rab3 GEP SNARE Rab3 GAP Rab3 GAP Rabphilin3 Tomsyn

项目摘要

There is a small G protein superfamily occurring in species from yeast to mammals and consisting of more than sixty members.Rab3A, a member of the small G protein superfamily, and its regulatory proteins, Rab3 GAP and Rab3 GEP, were discovered in our laboratory.Rab3A is involved in regulated secretion such as neurotransmitter release.During this support from 1997 to 1998, we have accumulated the evidence that these regulatory proteins play important roles in neurotransmitter release, and have furthermore found novel components of the neurotransmitter release machinery.The results obtained are as follows :(1) We have characterized GAP specific for the Rab3 subfamily including Rab3A, -B, -C, and -D.Rab3 GAP is a heterodimer consisting of p130, a catalytic subunit, and p150, a non catalytic subunit.Both the proteins are highly concentrated in the presynaptic nerve terminals.The study using the growth hormone (GH) co-expression assay system of PC12 cells indicates that both the proteins ar … More e indeed involved in Ca_<2+>-dependent exocytosis.(2) It has been shown that Munc18 interacts with syntaxin-1 and inhibits the formation of the SNARE complex.We have isolated a novel syntaxin-1-binding protein and named it Tomosyn.Tomosyn has at least three splicing isoforms (b-, m-, and s-Tomosyns).m- and s-Tomosyns are present in brain but b-Tomosyn is ubiquitously expressed.All the Tomosyn isoforms have a VAMP-like region on their C-terminal portion and bind to syntaxin-1 through their VAMP-like region on m-Tomosyn is capable of dissociating Munc18 from syntaxin-1 and forms a novel 10S complex with syntaxin-1, SNAP-25, and synaptotagmin, but not with VAMP.The study using the GH co-expression assay system of PC12 cells indicates that m-Tomosyn is indeed involved in Ca^<2+>-dependent exocytosis.Since accumulating evidence suggests that the Rab family regulates the formation of the SNARE complex, it is possible that Tomosyn is involved in the Rab3A-dependent process of neurotransmitter release. Less

从酵母到哺乳动物的物种中存在一个小的G蛋白超家族，由60多个成员组成。Rab3a，一个小的G蛋白超级家族的成员及其调节蛋白Rab3 GAP和RAB3 GEP，在我们的实验室中发现了诸如诸如神经疗法的释放，从而涉及这种疾病，从而涉及这种疾病。 regulatory proteins play important roles in neurotransmitter release, and have furthermore found novel components of the neurotransmitter release machinery.The results obtained are as follows :(1) We have characterized GAP specific for the Rab3 subfamily including Rab3A, -B, -C, and -D.Rab3 GAP is a heterodimer consisting of p130, a catalytic subunit, and p150，一种非催化亚基。蛋白质都高度集中在突触前神经终末中。使用生长马酮（GH）PC12细胞的共表达评估系统的研究都表明，蛋白质均为Ca__ <2+> - 依赖性杂质的蛋白质相互作用。复合物。我们已经隔离了一种新型的征毒素1结合蛋白，并将其命名为tomosyn.tomosyn至少具有三种剪接同工型（B-，M-和S-Tomosyn）.m-和S-Tomosyn。脑中存在于大脑中，但B-Tomosyn在B-tomosyn中无处不在。 Syntaxin-1通过其在M-Tomosyn上的鞋面样区域能够能够使Munc18与syntaxin-1解离，并形成一种与Syntaxin-1，Snap-25和Synaptotagmin的新颖的10S复合物，但与VAMPAGMIN相关。累积的证据表明，RAB家族调节了军鼓复合物的形成，tomosyn可能参与了依赖于Rab3a的神经递质释放过程。较少的