Syntaxin-1A binds to and modulates the Slo calcium-activated potassium channel via an interaction that excludes syntaxin binding to calcium channels
Syntaxin-1A binds to and modulates the Slo calcium-activated potassium channel via an interaction that excludes syntaxin binding to calcium channels
复制标题
DOI：
10.1152/jn.00789.2004
复制
发表时间：
2005-03-01
影响因子：
2.5
通讯作者：
Levitan, IB
中科院分区：
文献类型：
--
作者：
Cibulsky, SA;Fei, H;Levitan, IB
从其在突触前神经末梢的位置，大电导Ca2+激活K+通道，Slo。调节神经递质释放。已知控制神经递质释放的其他几个离子通道与神经递质释放机制的物理相互作用有关。例如，Ca(v)2.2 （n型）Ca2+通道结合并由syntaxin-1A和SNAP-25调节。此外，Slo和Ca(v)2.2的紧密并置被认为是两个通道之间功能耦合所必需的。这在神经元中得到了证明。我们报道Slo与syntaxin-1A有很强的关联。Slo和syntaxin-1A在转染的HEK293细胞和脑组织中均有明显的共免疫沉淀。然而，尽管syntaxin-1A和Ca(v)2.2的II-III环之间存在这种强相互作用和已知的关联，但这三种蛋白在转染的HEK293细胞中不会以三聚体复合物的形式共同免疫沉淀。slow -syntaxin- 1a共免疫沉淀不受[Ca2+]的显著影响。多个相对弱的相互作用可以归结为全长Slo与syntaxin-1A的紧密物理耦合：Slo的c端尾和SO-S - I环各自与syntaxin-1A共免疫沉淀。syntaxin-1A的存在导致Slo通道活性降低，这是由于在100 nM， 1 muM和10 muM Ca2+中激活的V-1/2增加，降低了1 muM Ca2+中的电压敏感性，并且在10 muM Ca2+中激活的速率较慢。Slo和syntaxin-1A相互作用的潜在生理后果包括通过调节Slo通道活性来增强兴奋性，以及由于syntaxin-1A与Ca(v)2.2 II-III环结合的破坏而减少神经递质释放。
From its position in presynaptic nerve terminals, the large conductance Ca2+-activated K+ channel, Slo. regulates neurotransmitter release. Several other ion channels known to control neurotransmitter release have been implicated in physical interactions with the neurotransmitter release machinery. For example, the Ca(v)2.2 (N-type) Ca2+ channel binds to and is modulated by syntaxin-1A and SNAP-25. Furthermore, a close juxtaposition of Slo and Ca(v)2.2 is presumed to be necessary for functional coupling between the two channels. which has been shown in neurons. We report that Slo exhibits a strong association with syntaxin-1A. Robust co-immunoprecipitation of Slo and syntaxin-1A occurs from transfected HEK293 cells as well as from brain. However, despite this strong interaction and the known association between syntaxin-1A and the II-III loop of Ca(v)2.2, these three proteins do not co-immunoprecipitate in a trimeric complex from transfected HEK293 cells. The Slo-syntaxin-1A co-immunoprecipitation is not significantly influenced by [Ca2+]. Multiple relatively weak interactions may sum up to a tight physical coupling of full-length Slo with syntaxin-1A: the C-terminal tail and the SO-S I loop of Slo each co-immunoprecipitate with syntaxin-1A. The presence of syntaxin-1A leads to reduced Slo channel activity due to an increased V-1/2 for activation in 100 nM, 1 muM, and 10 muM Ca2+ reduced voltage-sensitivity in 1 muM Ca2+, and slower rates of activation in 10 muM Ca2+. Potential physiological consequences of the interaction between Slo and syntaxin-1A include enhanced excitability through modulation of Slo channel activity and reduced neurotransmitter release due to disruption of syntaxin-1A binding to the Ca(v)2.2 II-III loop.