KCNE1是两个不同离子通道超家族的辅助亚基
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KCNE1是两个不同离子通道超家族的辅助亚基
2020-12-30 15:21

本期文章:《细胞》:Online/在线发表

法国尼斯大学Guillaume Sandoz研究组发现,KCNE1是两个不同离子通道超家族的辅助亚基。这一研究成果于2020年12月28日在线发表在国际学术期刊《细胞》上。

使用药理学、基因缺失和单分子荧光测定法,研究人员发现KCNE1满足TMEM16A氯化物通道真正辅助亚基的所有标准。令人惊讶的是,与KCNE1的组装将TMEM16A从钙依赖性离子通道转换为电压依赖性离子通道。重要的是,KCNE1的TMEM16A调节域内的临床相关遗传突变消除了TMEM16A的调节,这表明TMEM16A-KCNE1电流可能有助于遗传病理。总而言之,这些发现挑战了关于蛋白质复合物和离子通道分类的现有规则。

据介绍,在研究人类病理生理学的基因变异时,确定组成蛋白质复合物的亚基特异性至关重要。属于电压门控离子通道超家族的成孔α-亚基KCNQ1,与其β-辅助亚基KCNE1结合来产生缓慢的心脏钾电流,其功能障碍导致心律不齐。

附:英文原文

Title: KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies

Author: Pablo ávalos Prado, Stephanie Hfner, Yannick Comoglio, Brigitte Wdziekonski, Christophe Duranton, Bernard Attali, Jacques Barhanin, Guillaume Sandoz

Issue&Volume: 2020-12-28

Abstract: Determination of what is the specificity of subunits composing a protein complex isessential when studying gene variants on human pathophysiology. The pore-forming α-subunitKCNQ1, which belongs to the voltage-gated ion channel superfamily, associates to itsβ-auxiliary subunit KCNE1 to generate the slow cardiac potassium IKs current, whose dysfunction leads to cardiac arrhythmia. Using pharmacology, geneinvalidation, and single-molecule fluorescence assays, we found that KCNE1 fulfilsall criteria of a bona fide auxiliary subunit of the TMEM16A chloride channel, whichbelongs to the anoctamin superfamily. Strikingly, assembly with KCNE1 switches TMEM16Afrom a calcium-dependent to a voltage-dependent ion channel. Importantly, clinicallyrelevant inherited mutations within the TMEM16A-regulating domain of KCNE1 abolishthe TMEM16A modulation, suggesting that the TMEM16A-KCNE1 current may contribute toinherited pathologies. Altogether, these findings challenge the dogma of the specificityof auxiliary subunits regarding protein complexes and questions ion channel classification.

DOI: 10.1016/j.cell.2020.11.047

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31619-6

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Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216

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