Conformational switch of syntaxin-1 controls synaptic vesicle fusion
Conformational switch of syntaxin-1 controls synaptic vesicle fusion
复制标题
DOI：
10.1126/science.1163174
复制
发表时间：
2008-09-12
期刊：
影响因子：
56.9
通讯作者：
Sudhof, Thomas C.
中科院分区：
文献类型：
--
作者：
Gerber, Stefan H.;Rah, Jong-Cheol;Sudhof, Thomas C.
在突触囊泡融合过程中，可溶性N-乙基马来酰亚胺敏感因子-附着蛋白受体（SNARE）蛋白突触融合蛋白-1表现出两种与Munc 18 - 1结合的构象：SNARE复合物外的“闭合”构象和SNARE复合物内的“开放”构象.尽管含有开放型突触融合蛋白-1和Munc 18 - 1的SNARE复合物对于胞吐作用是必需的，但封闭型突触融合蛋白-1的功能尚不清楚。我们产生了敲入/敲除小鼠，只表达开放的syntaxin- 1B。Syntaxin- 1B（Open）小鼠存活，但在2至3个月大时死于全身性癫痫发作。结合Munc 18 - 1 syntaxin- 1受损syntaxin- 1B（开放）突触，容易释放的囊泡池的大小减少，但是，突触囊泡融合的速度显着增强。因此，突触融合蛋白-1的闭合构象控制了突触囊泡融合反应的起始，然后由SNARE-复合物/Munc 18 - 1组装体介导.
During synaptic vesicle fusion, the soluble N- ethylmaleimide- sensitive factor- attachment protein receptor ( SNARE) protein syntaxin- 1 exhibits two conformations that both bind to Munc18- 1: a "closed" conformation outside the SNARE complex and an "open" conformation in the SNARE complex. Although SNARE complexes containing open syntaxin- 1 and Munc18- 1 are essential for exocytosis, the function of closed syntaxin- 1 is unknown. We generated knockin/knockout mice that expressed only open syntaxin- 1B. Syntaxin- 1B(Open) mice were viable but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18- 1 to syntaxin- 1 was impaired in syntaxin- 1B(Open) synapses, and the size of the readily releasable vesicle pool was decreased; however, the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin- 1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE- complex/ Munc18- 1 assemblies.