SNARE complex formation is triggered by Ca2+ and drives membrane fusion
SNARE complex formation is triggered by Ca2+ and drives membrane fusion
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DOI：
10.1016/s0092-8674(00)80727-8
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发表时间：
1999-04-16
期刊：
影响因子：
64.5
通讯作者：
Scheller, RH
中科院分区：
文献类型：
--
作者：
Chen, YA;Scales, SJ;Scheller, RH
神经递质胞吐是一个由syntaxin、SNAP-25和VAMP （SNAREs）核心复合物介导的过程，可被切断SNAREs的神经毒素抑制。肉毒杆菌神经毒素E可以通过添加SNAP-25的65 aa c端片段（S25-C）来恢复对渗透性PC12细胞去甲肾上腺素释放的抑制。S25-C螺旋疏水性表面的突变导致具有不同热稳定性的SNARE复合物，这些突变体在不同程度上挽救胞外分泌。抢救取决于S25-C和Ca2+的持续存在，并与复合体的形成相关。数据表明，Ca2+触发S25-C结合到低亲和力位点，启动反式复合物的形成。SNARE蛋白在对抗膜上的配对导致双层融合，并产生高亲和力的顺式SNARE复合物。
Neurotransmitter exocytosis, a process mediated by a core complex of syntaxin, SNAP-25, and VAMP (SNAREs), is inhibited by SNARE-cleaving neurotoxins. Botulinum neurotoxin E inhibition of norepinephrine release in permeabilized PC12 cells can be rescued by adding a 65 aa C-terminal fragment of SNAP-25 (S25-C). Mutations along the hydrophobic face of the S25-C helix result in SNARE complexes with different thermostabilities, and these mutants rescue exocytosis to different extents. Rescue depends on the continued presence of both S25-C and Ca2+ and correlates with complex formation. The data suggest that Ca2+ triggers S25-C binding to a low-affinity site, initiating trans-complex formation. Pairing of SNARE proteins on apposing membranes leads to bilayer fusion and results in a high-affinity cis-SNARE complex.