Interactions of presynaptic Ca2+ channels and snare proteins in neurotransmitter release
Interactions of presynaptic Ca2+ channels and snare proteins in neurotransmitter release
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DOI：
10.1111/j.1749-6632.1999.tb11284.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Catterall, WA
中科院分区：
文献类型：
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作者：
Catterall, WA
N-和P/ q型Ca2+通道高密度定位于突触前神经末梢，是神经元兴奋-分泌耦合的关键因素。除了介导Ca2+进入以启动递质释放外，它们还被认为直接与突触囊泡对接/融合机制的蛋白质相互作用。此外，n型和P/ q型Ca2+通道与syntaxin在神经末梢的高密度簇中共定位，突触蛋白相互作用（syntaxin）位点在脑内的突触蛋白相互作用（synprint）位点。n型和P/ q型Ca2+通道α (1B)和α (1A)亚基的细胞内环II-LII （LII-III）与syntaxin， SNAP-25和synaptotagmin相关，Ca2+具有双相作用。n型Ca2+通道与SNARE复合物的相互作用，刺激10-30 μ M范围内的最佳结合，n型合成肽的PKC或CaM KII磷酸化抑制了与含有syntaxin和SNAP-25的SNARE复合物的相互作用。在生理Ca2+浓度下，在细胞培养中注射的青蛙神经肌肉接头中，synprint肽显著减少了递质释放，这与理论模型分析的70%的停泊囊泡前Ca2+通道脱离一致。总之，这些研究表明突触前Ca2+通道不仅提供胞外机制所需的Ca2+信号，而且还包含囊泡对接启动和融合过程中不可或缺的结构元件。
N- and P/Q-type Ca2+ channels are localized in high density in presynaptic nerve terminals and 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. These Ca2+ channels can he puri tied from brain as a complex with SNARE proteins, which are involved in exocytosis, In addition, N-type and P/Q-type Ca2+ channels are colocalized with syntaxin in high-density clusters in nerve terminals, The synaptic protein interaction (synprint) sites in the? intracellular loop II-LII (LII-III) of both alpha(1B) and alpha(1A) subunits of N-type and P/Q-type Ca2+ channels bmd to syntaxin, SNAP-25, and synaptotagmin, Ca2+ has a biphasic effect on the? interactions of N-type Ca2+ channels with SNARE complexes, stimulating optimal binding in the range of 10-30 mu M, PKC or CaM KII phosphorylation of the N-type synprint peptide inhibits interactions with SNARE complexes containing syntaxin and SNAP-25. Introduction of the synprint peptides into presynaptic superior cervical ganglion neurons reversibly inhibits EPSPs from synchronous transmitter release by 42%, At physiological Ca2+ concentrations, synprint peptides significantly reduce transmitter release in injected frog neuromuscular junctions in cell culture, consistent with detachment of 70% of the docked vesicles front Ca2+ channels as analyzed by a theoretical model. Together, these studies suggest that presynaptic Ca2+ channels not only provide the Ca2+ signal required by the exocytotic mechinery, but also contain structural elements that are integral to vesicle docking priming, and fusion processes.