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Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel
Review

Polymodal Control of TMEM16x Channels and Scramblases

Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
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Author to whom correspondence should be addressed.
Academic Editors: Anna Boccaccio and Simone Pifferi
Int. J. Mol. Sci. 2022, 23(3), 1580; https://doi.org/10.3390/ijms23031580
Received: 5 December 2021 / Revised: 20 January 2022 / Accepted: 20 January 2022 / Published: 29 January 2022
(This article belongs to the Special Issue Ca2+-Activated Chloride Channels and Phospholipid Scramblases)
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. View Full-Text
Keywords: Ca2+-activated Cl channels; anoctamin; TMEM16x; scramblases; lipids; gating; Ca2+ signalling; SARS-CoV-2 Ca2+-activated Cl channels; anoctamin; TMEM16x; scramblases; lipids; gating; Ca2+ signalling; SARS-CoV-2
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MDPI and ACS Style

Agostinelli, E.; Tammaro, P. Polymodal Control of TMEM16x Channels and Scramblases. Int. J. Mol. Sci. 2022, 23, 1580. https://doi.org/10.3390/ijms23031580

AMA Style

Agostinelli E, Tammaro P. Polymodal Control of TMEM16x Channels and Scramblases. International Journal of Molecular Sciences. 2022; 23(3):1580. https://doi.org/10.3390/ijms23031580

Chicago/Turabian Style

Agostinelli, Emilio, and Paolo Tammaro. 2022. "Polymodal Control of TMEM16x Channels and Scramblases" International Journal of Molecular Sciences 23, no. 3: 1580. https://doi.org/10.3390/ijms23031580

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