PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel

被引：104

作者：

Yang, Junhua ^{[1
]}

Chen, Jianan ^{[1
]}

Vitery, Maria del Carmen ^{[1
]}

Osei-Owusu, James ^{[1
]}

Chu, Jiachen ^{[1
]}

Yu, Haiyang ^{[2
]}

Sun, Shuying ^{[3
]}

Qiu, Zhaozhu ^{[1
,4
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[2] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pathol, Brain Sci Inst, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

来源：

SCIENCE | 2019年 / 364卷 / 6438期

关键词：

ANION CHANNELS; REVEALS; DEATH;

D O I：

10.1126/science.aav9739

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 PAC (TMEM206) as being essential for the widely observed proton-activated Cl- (PAC) currents (I-Cl,I-H). Overexpression of human PAC in PAC knockout cells generated I-Cl,I-H with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse Pac abolished I-Cl,I-H 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.

引用

页码：395 / +

页数：23

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