Modulatory mechanisms and multiple functions of somatodendritic A-type K (+) channel auxiliary subunits.
Modulatory mechanisms and multiple functions of somatodendritic A-type K (+) channel auxiliary subunits.
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DOI：
10.3389/fncel.2014.00082
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发表时间：
2014
影响因子：
5.3
通讯作者：
Pfaffinger PJ
中科院分区：
文献类型：
--
作者：
Jerng HH;Pfaffinger PJ
辅助亚基是多蛋白离子通道复合物的非传导性、调节性组分，是正常神经元信号传导的基础。它们与成孔α-亚基相互作用以调节表面分布、离子电导和通道门控特性。对于基于Kv 4 α-亚基的体树突阈下A型钾（伊萨）通道，两种类型的辅助亚基已被广泛研究：Kv通道相互作用蛋白（KChIP）和二肽基肽酶样蛋白（DPLP）。KChIP是与Kv 4亚基的细胞内部分相互作用的细胞质钙结合蛋白，而DPLPs是与Kv 4通道核心相关的II型跨膜蛋白。KChIP和DPLPs基因都含有多个起始位点，这些位点被各种神经元群体用来驱动功能不同的N-末端变体的差异表达。反过来，这些N-末端变体在整个神经系统中产生了巨大的功能多样性。在这里，我们集中我们的审查（1）的分子机制，不同的N-末端变体的独特性质，（2）塑造天然伊萨属性的协调行动的KChIPs和DPLP变体，和（3）令人惊讶的方式，KChIPs和DPLPs协调多个通道的活动，微调神经元的兴奋性。解开不同辅助亚基N-末端变体的独特贡献可能为开发新型靶向治疗药物以治疗多种神经系统疾病提供重要机会。
Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming α-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (ISA) channel based on Kv4 α-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPLPs). KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1) the molecular mechanism underlying the unique properties of different N-terminal variants, (2) the shaping of native ISA properties by the concerted actions of KChIPs and DPLP variants, and (3) the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders.
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影响因子：
4.8
作者：
Clark BD;Kwon E;Maffie J;Jeong HY;Nadal M;Strop P;Rudy B
通讯作者：
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30.8
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影响因子：
3.3
作者：
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