The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission

被引:113
作者
Stevens, CF
Sullivan, JM
机构
[1] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA
关键词
D O I
10.1016/S0896-6273(03)00432-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:299 / 308
页数:10
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