The KCNE2 K⁺ channel regulatory subunit: Ubiquitous influence, complex pathobiology.
The KCNE2 K⁺ channel regulatory subunit: Ubiquitous influence, complex pathobiology.
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DOI：
10.1016/j.gene.2015.06.061
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发表时间：
2015-09-15
期刊：
影响因子：
3.5
通讯作者：
Abbott GW
中科院分区：
文献类型：
--
作者：
Abbott GW
KCNE单跨膜亚基由人类和小鼠基因组中的5个成员基因家族编码。KCNE亚基主要被认为与电压门控钾通道共组装并在功能上调节，在哺乳动物生理学中广泛的影响掩盖了它们的小体积。自从我们首次发现KCNE2在心脏中的作用及其与遗传性和获得性人类长QT综合征的关系以来，KCNE2已被广泛研究。从那时起，生理学分析以及人类和小鼠遗传学研究已经揭示了KCNE2在心脏、胃、甲状腺和脉络膜丛中的一系列惊人功能。硬币的另一面是由KCNE2破坏引起的各种相互关联的疾病表现，包括可兴奋的细胞，如心肌细胞和不可兴奋的极化上皮。小鼠的Kcne2缺失在说明单基因心律失常综合征的潜在后果方面特别有用，移除一块揭示了这个谜题的意想不到的复杂性。在这里，我们回顾了KCNE2的功能和病理生物学的最新知识。
The KCNE single-span transmembrane subunits are encoded by five-member gene families in the human and mouse genomes. Primarily recognized for co-assembling with and functionally regulating the voltage-gated potassium channels, the broad influence of KCNE subunits in mammalian physiology belies their small size. KCNE2 has been widely studied since we first discovered one of its roles in the heart and its association with inherited and acquired human Long QT syndrome. Since then, physiological analyses together with human and mouse genetics studies have uncovered a startling array of functions for KCNE2, in the heart, stomach, thyroid and choroid plexus. The other side of this coin is the variety of interconnected disease manifestations caused by KCNE2 disruption, involving both excitable cells such as cardiomyocytes, and non-excitable, polarized epithelia. Kcne2 deletion in mice has been particularly instrumental in illustrating the potential ramifications within a monogenic arrhythmia syndrome, with removal of one piece revealing the unexpected complexity of the puzzle. Here, we review current knowledge of the function and pathobiology of KCNE2.