TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
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DOI：
10.1126/science.1163518
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发表时间：
2008-10-24
期刊：
影响因子：
56.9
通讯作者：
Galietta, Luis J. V.
中科院分区：
文献类型：
--
作者：
Caputo, Antonella;Caci, Emanuela;Galietta, Luis J. V.
钙依赖性氯离子通道是正常电解质和液体分泌、嗅觉以及神经元和平滑肌兴奋性所必需的。这些膜蛋白的分子身份仍不清楚。用白细胞介素 4 (IL-4) 处理支气管上皮细胞会导致钙依赖性氯离子通道活性增加，这可能是通过调节相应基因的表达来实现的。我们进行了全局基因表达分析，以确定受 IL-4 调节的膜蛋白。用针对这些蛋白质中的每一种的特异性小干扰RNA转染上皮细胞表明，TMEM16A（功能未知的推定质膜蛋白质家族的成员）与钙依赖性氯电流相关，通过卤化物敏感荧光蛋白、短路电流和膜片钳技术进行测量。我们的结果表明 TMEM16A 是钙依赖性氯离子通道的内在成分。鉴定与氯离子通道功能相关的先前未知的膜蛋白家族将提高我们对氯离子转运生理病理学的理解，并允许开发可用于基础研究和药物开发的药理学工具。
Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear. Treatment of bronchial epithelial cells with interleukin-4 (IL-4) causes increased calcium-dependent chloride channel activity, presumably by regulating expression of the corresponding genes. We performed a global gene expression analysis to identify membrane proteins that are regulated by IL-4. Transfection of epithelial cells with specific small interfering RNA against each of these proteins shows that TMEM16A, a member of a family of putative plasma membrane proteins with unknown function, is associated with calcium-dependent chloride current, as measured with halide-sensitive fluorescent proteins, short-circuit current, and patch-clamp techniques. Our results indicate that TMEM16A is an intrinsic constituent of the calcium-dependent chloride channel. Identification of a previously unknown family of membrane proteins associated with chloride channel function will improve our understanding of chloride transport physiopathology and allow for the development of pharmacological tools useful for basic research and drug development.