Physical Link and Functional Coupling of Presynaptic Calcium Channels and the Synaptic Vesicle Docking/Fusion Machinery
Physical Link and Functional Coupling of Presynaptic Calcium Channels and the Synaptic Vesicle Docking/Fusion Machinery
复制标题
突触前钙通道和突触小泡对接/融合机制的物理连接和功能耦合
DOI：
--
复制
发表时间：
1998
影响因子：
3
通讯作者：
W. Catterall
中科院分区：
文献类型：
--
作者：
Zu;R. Westenbroek;W. Catterall
N-和P/Q-型钙通道高密度地定位于突触前神经末梢，是神经元兴奋-分泌偶联的关键元件。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。如前所述，这些钙通道可以从脑中纯化，作为与参与胞吐作用的SNARE蛋白的复合物。此外，N型和P/Q型钙通道与突触融合蛋白共定位于神经末梢的高密度簇中。本文综述了N型和P/Q型钙通道α1B和α1A亚基的细胞内环II-III（LII-III）中突触蛋白相互作用（synprint）位点的作用，这些位点与突触融合蛋白、SNAP-25和突触结合蛋白结合。钙对N型钙通道与SNARE复合物的相互作用具有双相效应，在10-20 μM范围内刺激最佳结合。PKC或CaM KII磷酸化的N-型synprint肽抑制与天然脑SNARE复合物含有syntaxin和SNAP-25的相互作用。将synprint肽引入突触前上级颈神经节神经元可逆地抑制了42%的EPSP同步递质释放。在生理Ca 2+浓度下，synprint肽导致注射的青蛙神经肌肉接头在培养物中的递质释放减少约25%，与基于理论模型的70%的停靠囊泡从钙通道脱离一致。总之，这些研究表明，突触前钙离子通道不仅提供所需的胞吐机制的钙信号，但也包含的结构元件，是不可或缺的小泡对接，启动和融合过程。
N- and P/Q-type calcium 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. As outlined in the preceding article, these calcium channels can be purified from brain as a complex with SNARE proteins which are involved in exocytosis. In addition, N-type and P/Q-type calcium channels are co-localized with syntaxin in high-density clusters in nerve terminals. Here we review the role of the synaptic protein interaction (synprint) sites in the intracellular loop II–III (LII–III) of both α1B and α1A subunits of N-type and P/Q-type calcium channels, which bind to syntaxin, SNAP-25, and synaptotagmin. Calcium has a biphasic effect on the interactions of N-type calcium channels with SNARE complexes, stimulating optimal binding in the range of 10–20 μM. PKC or CaM KII phosphorylation of the N-type synprint peptide inhibits interactions with native brain 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 cause an approximate 25% reduction in transmitter release of injected frog neuromuscular junction in cultures, consistent with detachment of 70% of the docked vesicles from calcium channels based on a theoretical model. Together, these studies suggest that presynaptic calcium channels not only provide the calcium signal required by the exocytotic machinery, but also contain structural elements that are integral to vesicle docking, priming, and fusion processes.
影响因子：
56.9
作者：
LLINAS, R;SUGIMORI, M;SILVER, RB
通讯作者：
SILVER, RB
具有不同 COOH 末端的两种大小形式的 N 型钙通道 α 1 亚基的差异磷酸化。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hell,JW;Appleyard,SM;Yokoyama,CT;Warner,C;Catterall,WA
通讯作者：
Catterall,WA
影响因子：
56.9
作者：
WHEELER, DB;RANDALL, A;TSIEN, RW
通讯作者：
TSIEN, RW