SV2A and SV2C contain a unique synaptotagmin-binding site
SV2A and SV2C contain a unique synaptotagmin-binding site
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DOI：
10.1016/j.mcn.2004.12.011
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发表时间：
2005-05-01
影响因子：
3.5
通讯作者：
Bajjalieh, SM
中科院分区：
文献类型：
--
作者：
Schivell, AE;Mochida, S;Bajjalieh, SM
SV 2（突触囊泡蛋白2）在神经元和内分泌细胞中表达，在正常钙诱发的神经分泌中需要SV 2。在哺乳动物中，存在三种SV 2基因，表示为SV 2 A、B和C。SV 2A与synaptotagmin相互作用，synaptotagmin是胞吐中钙传感器的主要候选者。在这里，我们报告说，所有异构体的原生SV 2结合突触结合蛋白和钙抑制的结合，表明所有异构体含有一个共同的钙抑制突触结合蛋白结合位点。孤立的SV 2A和SV 2C的氨基末端支持一个额外的相互作用与synaptotagmin，并在该网站的结合刺激钙。氨基末端结合位点被映射到SV 2A的前57个氨基酸，并且去除该结构域降低了钙介导的对与突触结合蛋白的结合的抑制，表明其调节钙对SV 2-突触结合蛋白相互作用的影响。将SV 2A或SV 2C的氨基末端引入培养的上级颈神经节神经元中抑制神经传递，而SV 2B的氨基末端则不抑制。这些观察结果暗示SV 2-突触结合蛋白相互作用在调节胞吐作用，并表明SV 2A和SV 2C，通过其额外的突触结合蛋白结合位点，功能不同于SV 2B。(c)2005年爱思唯尔公司All rights reserved.
SV2 (Synaptic Vesicle Protein 2) is expressed in neurons and endocrine cells where it is required for normal calcium-evoked neurosecretion. In mammals, there are three SV2 genes, denoted SV2A, B and C. SV2A interacts with synaptotagmin, the prime candidate for the calcium sensor in exocytosis. Here, we report that all isoforms of native SV2 bind synaptotagmin and that binding is inhibited by calcium, indicating that all isoforms contain a common calcium-inhibited synaptotagmin-binding site. The isolated amino termini of SV2A and SV2C supported an additional interaction with synaptotagmin, and binding at this site was stimulated by calcium. The amino-terminal binding site was mapped to the first 57 amino acids of SV2A, and removal of this domain decreased calcium-mediated inhibition of binding to synaptotagmin, suggesting that it modulates calcium's effect on the SV2-synaptotagmin interaction. Introduction of the amino terminus of SV2A or SV2C into cultured superior cervical ganglion neurons inhibited neurotransmission, whereas the amino terminus of SV2B did not. These observations implicate the SV2-synaptotagmin interaction in regulated exocytosis and suggest that SV2A and SV2C, via their additional synaptotagmin binding site, function differently than SV2B. (c) 2005 Elsevier Inc. All rights reserved.