α-SNAP Interferes with the Zippering of the SNARE Protein Membrane Fusion Machinery
α-SNAP Interferes with the Zippering of the SNARE Protein Membrane Fusion Machinery
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DOI：
10.1074/jbc.m114.556803
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发表时间：
2014-06-06
影响因子：
4.8
通讯作者：
Jahn, Reinhard
中科院分区：
文献类型：
--
作者：
Park, Yongsoo;Vennekate, Wensi;Jahn, Reinhard
神经元胞吐作用由可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白介导。在融合之前，SNARE蛋白形成桥接膜的复合物，随后朝向C-末端膜锚组装，从而启动膜融合。融合后，SNARE复合物被AAA-ATP酶N-乙基马来酰亚胺敏感因子分解，该因子需要辅因子α-SNAP首先与组装的SNARE复合物结合。使用嗜铬颗粒和脂质体，我们现在表明，α-SNAP本身干扰拉链的膜锚定的陷阱复合物的拉链中途通过拉链反应，逮捕陷阱在一个部分组装的反式复合物，并防止融合。有趣的是，这种干扰不会对突触囊泡产生抑制作用，这表明膜的性质也会影响α-SNAP干扰SNARE拉链的最终结果。我们认为α-SNAP与SNARE复合物的结合影响SNARE复合物利用能量或向膜传递力的能力。
Neuronal exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Before fusion, SNARE proteins form complexes bridging the membrane followed by assembly toward the C-terminal membrane anchors, thus initiating membrane fusion. After fusion, the SNARE complex is disassembled by the AAA-ATPase N-ethylmaleimide-sensitive factor that requires the cofactor alpha-SNAP to first bind to the assembled SNARE complex. Using chromaffin granules and liposomes we now show that alpha-SNAP on its own interferes with the zippering of membrane-anchored SNARE complexes midway through the zippering reaction, arresting SNAREs in a partially assembled trans-complex and preventing fusion. Intriguingly, the interference does not result in an inhibitory effect on synaptic vesicles, suggesting that membrane properties also influence the final outcome of alpha-SNAP interference with SNARE zippering. We suggest that binding of alpha-SNAP to the SNARE complex affects the ability of the SNARE complex to harness energy or transmit force to the membrane.