PAC，一种进化上保守的膜蛋白，是一种质子激活的氯离子通道。
PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel.
机构信息
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA.
出版信息
Science. 2019 Apr 26;364(6438):395-399. doi: 10.1126/science.aav9739. Epub 2019 Apr 25.
Abstract
Severe local acidosis causes tissue damage and pain, and is one of the hallmarks of many diseases including ischemia, cancer, and inflammation. However, the molecular mechanisms of the cellular response to acid are not fully understood. We performed an unbiased RNA interference screen and identified as being essential for the widely observed proton-activated Cl (PAC) currents ( ). Overexpression of human PAC in knockout cells generated with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse abolished in neurons and attenuated brain damage after ischemic stroke. The wide expression of PAC suggests a broad role for this conserved Cl channel family in physiological and pathological processes associated with acidic pH.
摘要
严重的局部酸中毒会导致组织损伤和疼痛，是包括缺血、癌症和炎症在内的许多疾病的特征之一。然而，细胞对酸的反应的分子机制尚不完全清楚。我们进行了一项无偏 RNA 干扰筛选，发现 对于广泛观察到的质子激活 Cl（PAC）电流（）是必需的。在 敲除细胞中过表达人 PAC 会产生与内源性 PAC 电流具有相同特征的电流。斑马鱼 PAC 编码具有独特特性的 PAC 通道。敲除小鼠 会导致神经元中的 消失，并减轻缺血性中风后的脑损伤。PAC 的广泛表达表明，这种保守的 Cl 通道家族在与酸性 pH 值相关的生理和病理过程中具有广泛的作用。
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