Loading…

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

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...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2019-04, Vol.364 (6438), p.395-399
Main Authors: Yang, Junhua, Chen, Jianan, Del Carmen Vitery, Maria, Osei-Owusu, James, Chu, Jiachen, Yu, Haiyang, Sun, Shuying, Qiu, Zhaozhu
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aav9739