Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25.
Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25.
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脑 Ca2 通道的 α1A 亚基与突触前蛋白 Syntaxin 和 SNAP-25 的异构体特异性相互作用。
DOI：
10.1073/pnas.93.14.7363
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发表时间：
1996
影响因子：
11.1
通讯作者：
Catterall,WA
中科院分区：
文献类型：
--
作者：
Rettig,J;Sheng,ZH;Kim,DK;Hodson,CD;Snutch,TP;Catterall,WA
突触前Ca ~（2+）通道是神经元兴奋-分泌偶联的重要组成部分。除了介导Ca 2+进入以启动递质释放之外，它们被认为直接与突触囊泡对接/融合机制的蛋白质相互作用。在这里，我们报告亚型特异性，化学计量相互作用的BI和rbA亚型的α 1A亚基的P/Q型钙离子通道与突触前膜蛋白syntaxin和SNAP-25在体外和大鼠脑细胞膜。BI同种型与两种蛋白质结合，而rbA同种型在体外仅可检测到与SNAP-25的相互作用。突触蛋白相互作用（“synprint”）位点涉及连接BI序列的氨基酸残基722和1036之间的结构域II和III的胞内环的两个相邻片段。这种相互作用被N型Ca 2+通道的相应区域竞争性阻断，表明这两个通道与突触融合蛋白和SNAP-25的重叠区域结合。我们的研究结果提供了一个分子基础之间的物理联系Ca 2+流入神经末梢和随后的神经递质的胞吐作用在突触，突触前Ca 2+通道含有α 1A亚基。
Presynaptic Ca2+ channels are crucial elements in neuronal excitation-secretion coupling. In addition to mediating Ca2+ entry to initiate transmitter release, they are thought to interact directly with proteins of the synaptic vesicle docking/fusion machinery. Here we report isoform-specific, stoichiometric interaction of the BI and rbA isoforms of the alpha1A subunit of P/Q-type Ca2+ channels with the presynaptic membrane proteins syntaxin and SNAP-25 in vitro and in rat brain membranes. The BI isoform binds to both proteins, while only interaction with SNAP-25 can be detected in vitro for the rbA isoform. The synaptic protein interaction ("synprint") site involves two adjacent segments of the intracellular loop connecting domains II and III between amino acid residues 722 and 1036 of the BI sequence. This interaction is competitively blocked by the corresponding region of the N-type Ca2+ channel, indicating that these two channels bind to overlapping regions of syntaxin and SNAP-25. Our results provide a molecular basis for a physical link between Ca2+ influx into nerve terminals and subsequent exocytosis of neurotransmitters at synapses that have presynaptic Ca2+ channels containing alpha1A subunits.