The neuronal Kv4 channel complex
The neuronal Kv4 channel complex
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DOI：
10.1007/s11064-008-9650-8
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发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Wang, Guangyu
中科院分区：
文献类型：
--
作者：
Covarrubias, Manuel;Bhattacharji, Aditya;Wang, Guangyu
Kv4 通道复合物介导神经元体细胞树突 A 型 K+ 电流 (I-SA)，在树突信号整合中发挥关键作用。这些复合物由成孔电压门控 α 亚基 (Shal/Kv4) 和至少两类辅助 β 亚基组成：KChIP（K+ 通道相互作用蛋白）和 DPLP（二肽基肽酶样蛋白）。在这里，我们回顾了对 Kv4 门控机制和特定辅助 β 亚基功能重塑的研究。也就是说，我们得出的结论是：（1）Kv4通道复合体采用了新型的封闭状态失活替代机制； (2) T1 结构域中的细胞内 Zn2+ 位点发生与电压依赖性门控紧密耦合的构象变化，并成为亚硝化调节的目标； (3)离散且特定的相互作用介导KChIPs和DPLPs对Kv4通道的激活、失活和渗透的影响。这些研究为 I-SA 功能和调节的分子基础提供了新的线索。
Kv4 channel complexes mediate the neuronal somatodendritic A-type K+ current (I-SA), which plays pivotal roles in dendritic signal integration. These complexes are composed of pore-forming voltage-gated alpha-subunits (Shal/Kv4) and at least two classes of auxiliary beta-subunits: KChIPs (K+-Channel-Interacting-Proteins) and DPLPs (Dipeptidyl-Peptidase-Like-Proteins). Here, we review our investigations of Kv4 gating mechanisms and functional remodeling by specific auxiliary beta-subunits. Namely, we have concluded that: (1) the Kv4 channel complex employs novel alternative mechanisms of closed-state inactivation; (2) the intracellular Zn2+ site in the T1 domain undergoes a conformational change tightly coupled to voltage-dependent gating and is targeted by nitrosative modulation; and (3) discrete and specific interactions mediate the effects of KChIPs and DPLPs on activation, inactivation and permeation of Kv4 channels. These studies are shedding new light on the molecular bases of I-SA function and regulation.