Direct interaction of a brain voltage-gated K+ channel with syntaxin 1A:: Functional impact on channel gating
Direct interaction of a brain voltage-gated K+ channel with syntaxin 1A:: Functional impact on channel gating
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DOI：
10.1523/jneurosci.21-06-01964.2001
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发表时间：
2001-03-15
影响因子：
5.3
通讯作者：
Lotan, I
中科院分区：
文献类型：
--
作者：
Fili, O;Michaelevski, I;Lotan, I
突触前电压门控性K+（Kv）通道通过其塑造突触前动作电位的能力在调节递质释放中发挥生理作用。然而，这些通道与胞吐器直接相互作用的可能性从未被研究过。我们报告了脑突触体中Kv α 1.1和Kv β亚基与突触融合蛋白1A之间存在的物理相互作用，至少部分发生在含有突触融合蛋白，突触结合蛋白和SNAP-25的大分子复合物的背景下。在刺激神经递质释放后，这种相互作用发生了改变。通过突触融合蛋白的过表达和反义敲减，进一步表征了爪蟾卵母细胞中与突触融合蛋白的相互作用。突触融合蛋白与通道蛋白的直接物理相互作用导致Kv1.1/Kv β 1.1通道的快速失活程度增加。突触融合蛋白也影响通道的振幅在一个双相的方式，这取决于它的浓度。在低的突触融合蛋白浓度下，振幅显著增加，细胞表面通道表达没有可检测到的变化。然而，在较高的浓度，幅度下降，可能是因为伴随着细胞表面通道表达的减少，与突触融合蛋白在调节囊泡贩运的作用一致。所观察到的突触融合蛋白1A和Kv通道之间的物理和功能相互作用可能在突触功效和神经元兴奋性中发挥作用。
Presynaptic voltage-gated K+ (Kv) channels play a physiological role in the regulation of transmitter release by virtue of their ability to shape presynaptic action potentials. However, the possibility of a direct interaction of these channels with the exocytotic apparatus has never been examined. We report the existence of a physical interaction in brain synaptosomes between Kv alpha1.1 and Kv beta subunits with syntaxin 1A, occurring, at least partially, within the context of a macromolecular complex containing syntaxin, synaptotagmin, and SNAP-25. The interaction was altered after stimulation of neurotransmitter release. The interaction with syntaxin was further characterized in Xenopus oocytes by both overexpression and antisense knockdown of syntaxin. Direct physical interaction of syntaxin with the channel protein resulted in an increase in the extent of fast inactivation of the Kv1.1/Kv beta1.1 channel. Syntaxin also affected the channel amplitude in a biphasic manner, depending on its concentration. At low syntaxin concentrations there was a significant increase in amplitudes, with no detectable change in cell-surface channel expression. At higher concentrations, however, the amplitudes decreased, probably because of a concomitant decrease in cell-surface channel expression, consistent with the role of syntaxin in regulation of vesicle trafficking. The observed physical and functional interactions between syntaxin 1A and a Kv channel may play a role in synaptic efficacy and neuronal excitability.