Polymodal Control of TMEM16x Channels and Scramblases.
Int J Mol Sci
; 23(3)2022 Jan 29.
Article
in English
| MEDLINE | ID: covidwho-1667194
ABSTRACT
The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors-including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins-also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Chloride Channels
/
Anoctamins
/
Anoctamin-1
Limits:
Animals
/
Humans
Language:
English
Year:
2022
Document Type:
Article
Affiliation country:
Ijms23031580
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