PUBLICATION
PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel
- Authors
- Yang, J., Chen, J., Del Carmen Vitery, M., Osei-Owusu, J., Chu, J., Yu, H., Sun, S., Qiu, Z.
- ID
- ZDB-PUB-190427-5
- Date
- 2019
- Source
- Science (New York, N.Y.) 364: 395-399 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Cell Death
- Chloride Channels/classification
- Chloride Channels/genetics
- Chloride Channels/metabolism*
- Chlorides/metabolism
- Conserved Sequence
- Evolution, Molecular
- HEK293 Cells
- Humans
- Hydrogen-Ion Concentration
- Hypoxia-Ischemia, Brain/metabolism
- Hypoxia-Ischemia, Brain/pathology
- Membrane Proteins/classification
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Mice
- Mice, Knockout
- Neurons/metabolism
- Neurons/pathology
- Phylogeny
- RNA Interference
- Stroke/metabolism
- Stroke/pathology
- Zebrafish
- PubMed
- 31023925 Full text @ Science
Citation
Yang, J., Chen, J., Del Carmen Vitery, M., Osei-Owusu, J., Chu, J., Yu, H., Sun, S., Qiu, Z. (2019) PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel. Science (New York, N.Y.). 364:395-399.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping