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

小G蛋白超家族存在于从酵母到哺乳动物的物种中，由60多个成员组成。小G蛋白超家族成员Rab3A及其调节蛋白Rab3 GAP和Rab3 GEP是本实验室发现的。 Rab3A参与神经递质释放等调节分泌。在1997年至1998年的支持期间，我们积累了这些调节蛋白在神经递质中发挥重要作用的证据获得的结果如下：(1)我们表征了Rab3亚家族特异的GAP，包括Rab3A、-B、-C和-D。Rab3 GAP是由催化亚基 p130 和非催化亚基 p150 组成的异二聚体。这两种蛋白质都高度集中在突触前神经末梢。该研究使用PC12细胞的生长激素（GH）共表达测定系统表明，这两种蛋白确实参与了Ca_<2+>依赖性胞吐作用。（2）已表明Munc18与syntaxin-1和syntaxin-1相互作用。抑制 SNARE 复合体的形成。我们分离出一种新的 Syntaxin-1 结合蛋白，并将其命名为 Tomosyn。Tomosyn 至少有 3 种剪接异构体（b-、m- 和m-和 s-Tomosyn 存在于大脑中，但 b-Tomosyn 普遍表达。所有 Tomosyn 亚型在其 C 末端部分都有一个 VAMP 样区域，并通过其 VAMP 样结合到 Syntaxin-1 m-Tomosyn 上的区域能够将 Munc18 与 Syntaxin-1 分离，并与 Syntaxin-1 形成新型 10S 复合物， SNAP-25 和突触结合蛋白，但不与 VAMP 一起使用。使用 PC12 细胞 GH 共表达测定系统的研究表明 m-Tomosyn 确实参与 Ca^2+ 依赖性胞吐作用。因为越来越多的证据表明， Rab 家族调节 SNARE 复合体的形成，Tomosyn 可能参与 Rab3A 依赖性神经递质释放过程。