Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process
Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process
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DOI：
10.1016/s0896-6273(00)80472-9
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发表时间：
1998-05-01
期刊：
影响因子：
16.2
通讯作者：
Takai, Y
中科院分区：
文献类型：
--
作者：
Fujita, Y;Shirataki, H;Takai, Y
Syntaxin-1 是神经末梢突触小泡对接和/或膜融合可溶性 N-乙基马来酰亚胺敏感因子附着受体 (SNARE) 复合物（75 和 20S 复合物）的组成部分，Syntaxin-1 还与 Munc18/n-Sec1/rbSec1 形成异二聚体，该复合物不同于 75 和 20S 复合物。在本报告中，我们鉴定了一种新型的 Syntaxin-1 结合蛋白 Tomosyn，它能够将 Munc18 从 Syntaxin-1 上解离，并与 Syntaxin-1、可溶性 N-乙基马来酰亚胺敏感因子附着 (SNAP) 25 和突触结合蛋白形成新型 10S 复合物。 Tomosyn 的 130 kDa 同工型在大脑中特异性表达，其分布与神经末梢中的 Syntaxin-1 部分重叠。 Syntaxin-1 或 tomosyn 的高水平表达会导致 PC12 细胞的 Ca2+ 依赖性胞吐作用特异性减少。这些结果表明 Tomosyn 是神经递质释放过程中的重要组成部分，它可能刺激 SNARE 复合体的形成。
Syntaxin-1 is a component of the synaptic vesicle docking and/or membrane fusion soluble N-etyhlmaleimide-sensitive factor attachment receptor (SNARE) complex (75 and 20S complexes) in nerve terminals, Syntaxin-1 also forms a heterodimer with Munc18/n-Sec1/rbSec1 in a complex that is distinct from the 75 and 20S complexes. In this report, we identify a novel syntaxin-1-binding protein, tomosyn, that is capable of dissociating Munc18 from syntaxin-1 and forming a novel 10S complex with syntaxin-1, soluble N-etyhlmaleimide-sensitive factor attachment (SNAP) 25, and synaptotagmin. The 130 kDa isoform of tomosyn is specifically expressed in brain, where its distribution partly overlaps with that of syntaxin-1 in nerve terminals. High level expression of either syntaxin-1 or tomosyn results in a specific reduction in Ca2+-dependent exocytosis from PC12 cells. These results suggest that tomosyn is an important component in the neurotransmitter release process where it may stimulate SNARE complex formation.