Calmodulin regulation of TMEM16A and 16B Ca(2+)-activated chloride channels.
Calmodulin regulation of TMEM16A and 16B Ca(2+)-activated chloride channels.
复制标题
钙调蛋白对 TMEM16A 和 16B Ca(2 ) 激活的氯离子通道的调节。
DOI：
10.1080/19336950.2015.1058455
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Colecraft,HenryM
中科院分区：
文献类型：
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作者：
Yang,Tingting;Colecraft,HenryM
由TMEM16A和16B编码的Ca2+激活的氯离子通道在调节上皮粘液分泌、心脏和神经元兴奋性、平滑肌收缩、嗅觉传导和细胞增殖中起重要作用。Ca2+传感器calmodulin （CaM）是否以及如何调节TMEM16A和16B通道的活性一直是有争议的，也是一个持续争论的主题。最近，我们使用一种被称为ChIMP（相关蛋白的膜系固诱导的通道失活）的生物工程方法，认为在活细胞中，无Ca2+ CaM （apoCaM）与功能TMEM16A和16B通道复合物预先相关。此外，预关联的apoCaM介导一些TMEM16A剪接变体的Ca2+依赖性敏化活化（CDSA）和Ca2+依赖性失活（CDI）。在这篇综述中，我们在之前和最近的研究结果的背景下讨论了这些发现，这些结果与TMEM16A/16B通道的Ca2+依赖性调节和CaM的假定作用有关。我们进一步讨论了这些关于TMEM16A/16B通道的apoCaM调控的潜在未来方向，并指出这些未来的努力将极大地受益于David T. Yue博士及其同事在电压依赖性钙通道的CaM调控方面的开创性工作。
Ca2+-activated chloride channels encoded by TMEM16A and 16B are important for regulating epithelial mucus secretion, cardiac and neuronal excitability, smooth muscle contraction, olfactory transduction, and cell proliferation. Whether and how the ubiquitous Ca2+sensor calmodulin (CaM) regulates the activity of TMEM16A and 16B channels has been controversial and the subject of an ongoing debate. Recently, using a bioengineering approach termed ChIMP (Channel Inactivation induced by Membrane-tethering of an associated Protein) we argued that Ca2+-free CaM (apoCaM) is pre-associated with functioning TMEM16A and 16B channel complexes in live cells. Further, the pre-associated apoCaM mediates Ca2+-dependent sensitization of activation (CDSA) and Ca2+-dependent inactivation (CDI) of some TMEM16A splice variants. In this review, we discuss these findings in the context of previous and recent results relating to Ca2+-dependent regulation of TMEM16A/16B channels and the putative role of CaM. We further discuss potential future directions for these nascent ideas on apoCaM regulation of TMEM16A/16B channels, noting that such future efforts will benefit greatly from the pioneering work of Dr. David T. Yue and colleagues on CaM regulation of voltage-dependent calcium channels.