Conformational switch of syntaxin-1 controls synaptic vesicle fusion

被引：223

作者：

Gerber, Stefan H. ^{[3
]}

Rah, Jong-Cheol ^{[1
,2
,4
]}

Min, Sang-Won ^{[3
]}

Liu, Xinran ^{[3
,5
]}

de Wit, Heidi ^{[6
]}

Dulubova, Irina

Meyer, Alexander C. ^{[4
]}

Rizo, Josep ^{[7
]}

Arancillo, Marife ^{[1
,2
]}

Hammer, Robert E. ^{[7
]}

Verhage, Matthijs ^{[6
]}

Rosenmund, Christian ^{[1
,2
,4
]}

Sudhof, Thomas C. ^{[3
,5
,8
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA

[4] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany

[5] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

[6] Vrije Univ Amsterdam, Dept Funct Genom, NL-1081 BT Amsterdam, Netherlands

[7] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[8] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2008年 / 321卷 / 5895期

关键词：

D O I：

10.1126/science.1163174

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1507 / 1510

页数：4

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