The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission
The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission
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DOI：
10.1016/s0896-6273(03)00432-x
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发表时间：
2003-07-17
期刊：
影响因子：
16.2
通讯作者：
Sullivan, JM
中科院分区：
文献类型：
--
作者：
Stevens, CF;Sullivan, JM
突触结合蛋白是一种突触囊泡蛋白，被认为是负责突触快速释放神经递质的钙传感器。突触结合蛋白的两个C2结构域，C2A和C2B，每个都提供了一个钙结合口袋，里面有五个保守的谷氨酸盐贡献的负电荷。我们发现，即使当所有的C2A的保守的谷氨酸被中和替换与天冬酰胺，神经递质的释放仍然发生在海马突触文化。由于胞吐作用继续依赖于细胞外钙浓度，C2A结构域不能代表整个钙传感器。然而，C2A似乎确实是钙传感器的一部分，因为D232的取代改变了释放的钙依赖性，可能是通过减少必须结合以触发胞吐的钙离子的数量。我们的结论是，通过钙离子的配位来中和D232处的负电荷对于哺乳动物中枢神经系统突触的快速神经传递是必要的，但还不够。
Synaptotagmin is a synaptic vesicle protein that has been proposed to be the calcium sensor responsible for fast neurotransmitter release at synapses. Synaptotagmin's two C2 domains, C2A and C2B, each provide a calcium binding pocket lined with negative charges contributed by five conserved aspartates. We find that even when all of C2A's conserved aspartates are neutralized by replacement with asparagines, neurotransmitter release still occurs at hippocampal synapses in culture. Because exocytosis continues to be dependent on extracellular calcium concentration, the C2A domain cannot represent the entire calcium sensor. C2A does appear to be part of the calcium sensor, however, because substitution of D232 alters the calcium dependence of release, perhaps by reducing the number of calcium ions that must bind to trigger exocytosis. We conclude that neutralization of the negative charge at D232 by coordination of a calcium ion is necessary-but not sufficient-for fast neurotransmission at mammalian CNS synapses.