TMEM16A confers receptor-activated calcium-dependent chloride conductance
TMEM16A confers receptor-activated calcium-dependent chloride conductance
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DOI：
10.1038/nature07313
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发表时间：
2008-10-30
期刊：
影响因子：
64.8
通讯作者：
Oh, Uhtaek
中科院分区：
文献类型：
--
作者：
Yang, Young Duk;Cho, Hawon;Oh, Uhtaek
钙 (Ca2+) 激活的氯离子通道是许多生理过程的基本介质，包括跨上皮分泌、心脏和神经元兴奋、感觉转导、平滑肌收缩和受精。尽管它们具有重要的生理意义，但它们的分子特性仍然很大程度上未知。在这里，我们证明跨膜蛋白 16A（TMEM16A，我们也称为 anoctamin 1 (ANO1)）是一种真正的 Ca2+ 激活的氯通道，由细胞内 Ca2+ 和 Ca2+- 动员刺激激活。 ANO1 具有八个假定的跨膜结构域，并且与之前表征的通道没有明显的相似性，因此定义了一个新的离子通道家族。 ANO1 的生物物理特性和药理学特征与天然 Ca2+ 激活的氯电流完全一致。 ANO1 在各种分泌上皮、视网膜和感觉神经元中表达。此外，小鼠 Ano1 的敲低显着减少了天然 Ca2+ 激活的氯离子电流以及小鼠唾液的产生。我们得出结论，ANO1 是一种候选 Ca2+ 激活氯离子通道，可在多种生理过程中介导受体激活氯离子电流。
Calcium (Ca2+)-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A(TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca2+-activated chloride channel that is activated by intracellular Ca2+ and Ca2+- mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca2+- activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca2+-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca2+-activated chloride channel that mediates receptor- activated chloride currents in diverse physiological processes.