Function and action of Rab3A in neurotransmitter release

从酵母到哺乳动物都有一个小G蛋白超家族，由60多个成员组成。本实验室发现了小G蛋白超家族成员Rab3A及其调控蛋白Rab3GAP和Rab3GEP。Rab3A参与神经递质释放等调节分泌。在1997-1998年的支持中，我们积累了这些调节蛋白在神经递质释放中发挥重要作用的证据，并进一步发现了神经递质释放机制的新成分。结果如下：(1)我们鉴定了Rab3A、-B、-C、GEP等Rab3亚家族特有的GAP。和-D.Rab3GAP是一种由催化亚基P130和非催化亚基P150组成的异源二聚体。这两种蛋白都高度集中在突触前神经末梢。利用生长激素(GH)共表达系统对PC12细胞的研究表明，这两种蛋白都是…更多的人确实参与了Ca_&lt；2&gt；(2)已发现Munc18与Synaxin-1相互作用并抑制SNARE复合体的形成。我们分离到一种新的Synaxin-1结合蛋白，命名为TomSync。Tomosyn至少有三种剪接异构体(b-，m-，所有Tomosyns的C端都有一个VAMP样区域，并通过m-Tomosyn上的VAMP样区域与Synaxin-1结合，m-Tomosyns能够使Munc18与Synaxin-1解离，并与Synaxin-1、SNAP-25和Synaptoagmin形成一个新的10S复合体，但不与VAMP形成一个新的10S复合体。由于越来越多的证据表明，Rab家族调控着SNARE复合体的形成，因此Tomosyn可能参与了依赖Rab3A的神经递质释放过程。较少

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