Distinct domains of complexin I differentially regulate neurotransmitter release.
Distinct domains of complexin I differentially regulate neurotransmitter release.
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DOI：
10.1038/nsmb1292
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发表时间：
2007-10
影响因子：
16.8
通讯作者：
Rosenmund C
中科院分区：
文献类型：
--
作者：
Xue M;Reim K;Chen X;Chao HT;Deng H;Rizo J;Brose N;Rosenmund C
复合蛋白构成了四个突触高亲和力SNARE复合物结合蛋白的家族。他们积极调节后期，启动后的步骤，在Ca 2+触发的同步神经递质释放，但潜在的分子机制尚不清楚。我们在这里表明，复杂蛋白I通过其中央α-螺旋的SNARE复合物结合是必要的，但出乎意料地不足以促进神经递质释放的关键功能。SNARE复合物结合区的辅助α-螺旋N-末端在快速突触胞吐中起抑制作用，而其N-末端相邻序列即使在不存在Ca 2+传感器Synaptotagmin 1的情况下也促进Ca 2+触发的释放。我们的研究结果表明，不同的功能域的复合蛋白差异调节突触胞吐，并通过这些域之间的相互作用，复合蛋白发挥了至关重要的作用，微调钙触发的快速神经递质释放。
Complexins constitute a family of four synaptic high-affinity SNARE complex binding proteins. They positively regulate a late, post-priming step in Ca2+-triggered synchronous neurotransmitter release, but the underlying molecular mechanisms are unclear. We show here that SNARE complex binding of Complexin I via its central α-helix is necessary but unexpectedly not sufficient for its key function in promoting neurotransmitter release. An accessory α-helix N-terminal of the SNARE complex binding region plays an inhibitory role in fast synaptic exocytosis, while its N-terminally adjacent sequences facilitate Ca2+-triggered release even in the absence of the Ca2+ sensor Synaptotagmin 1. Our results indicate that distinct functional domains of Complexins differentially regulate synaptic exocytosis, and that via the interplay between these domains Complexins play a crucial role in fine-tuning Ca2+-triggered fast neurotransmitter release.