TY - JOUR
T1 - PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel
AU - Yang, Junhua
AU - Chen, Jianan
AU - Del Carmen Vitery, Maria
AU - Osei-Owusu, James
AU - Chu, Jiachen
AU - Yu, Haiyang
AU - Sun, Shuying
AU - Qiu, Zhaozhu
N1 - Publisher Copyright:
© 2019 American Association for the Advancement of Science. All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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 (ICl,H). Overexpression of human PAC in PAC knockout cells generated ICl,H with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse Pac abolished ICl,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.
AB - 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 (ICl,H). Overexpression of human PAC in PAC knockout cells generated ICl,H with the same characteristics as the endogenous ones. Zebrafish PAC encodes a PAC channel with distinct properties. Knockout of mouse Pac abolished ICl,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.
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U2 - 10.1126/science.aav9739
DO - 10.1126/science.aav9739
M3 - Article
C2 - 31023925
AN - SCOPUS:85065447718
SN - 0036-8075
VL - 364
SP - 395
EP - 399
JO - Science
JF - Science
IS - 6438
ER -