TMEM16 proteins: the long awaited calcium-activated chloride channels?

TMEM16 proteins: the long awaited calcium-activated chloride channels?
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DOI:
10.1590/s0100-879x2009005000028
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发表时间:
2009-11-01
影响因子:
2.3
通讯作者:
Niemeyer, M.I.
Niemeyer, M.I.
中科院分区:
医学4区
文献类型:
--
作者:
Flores, C.A.;Cid, L.P.;Niemeyer, M.I.

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首次在非洲爪蟾卵母细胞中观察到的钙激活氯离子通道(CaCCs)介导的电流已在许多细胞和组织中记录,从不同类型的神经元到上皮细胞和肌肉细胞。CaCC在神经元(包括感觉受体)的兴奋性调节中起作用。此外,它们是上皮细胞中氯离子运动的重要介质,其活性调节电解质和液体转运。CaCCs的作用,特别是在上皮细胞中,简要回顾了其在分泌上皮细胞中的功能。最近的鉴定由三个独立的小组,使用不同的策略,TMEM16A的分子对应的CaCC进行了讨论。TMEM16A是一个家族的一部分,在小鼠中有10个其他成员。潜在的TMEM16阴离子通道活性的发现为这些阴离子通道在特定细胞和器官生理学和病理生理学中的作用的分子研究开辟了道路。TMEM16A蛋白作为CaCC氯离子通道分子的鉴定代表了科学毅力和独创性的巨大胜利。三个独立研究小组所使用的不同方法也预示着这一发现的可靠性。
Currents mediated by calcium-activated chloride channels (CaCCs), observed for the first time in Xenopus oocytes, have been recorded in many cells and tissues ranging from different types of neurons to epithelial and muscle cells. CaCCs play a role in the regulation of excitability in neurons including sensory receptors. In addition, they are crucial mediators of chloride movements in epithelial cells where their activity regulates electrolyte and fluid transport. The roles of CaCCs, particularly in epithelia, are briefly reviewed with emphasis on their function in secretory epithelia. The recent identification by three independent groups, using different strategies, of TMEM16A as the molecular counterpart of the CaCC is discussed. TMEM16A is part of a family that has 10 other members in mice. The discovery of the potential TMEM16 anion channel activity opens the way for the molecular investigation of the role of these anion channels in specific cells and in organ physiology and pathophysiology. The identification of TMEM16A protein as a CaCC chloride channel molecule represents a great triumph of scientific perseverance and ingenuity. The varied approaches used by the three independent research groups also augur well for the solidity of the discovery.