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Anoctamin-4 is a bona fide Ca(2+)-dependent non-selective cation channel

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Item Type:Article
Title:Anoctamin-4 is a bona fide Ca(2+)-dependent non-selective cation channel
Creators Name:Reichhart, N. and Schöberl, S. and Keckeis, S. and Alfaar, A.S. and Roubeix, C. and Cordes, M. and Crespo-Garcia, S. and Haeckel, A. and Kociok, N. and Föckler, R. and Fels, G. and Mataruga, A. and Rauh, R. and Milenkovic, V.M. and Zühlke, K. and Klussmann, E. and Schellenberger, E. and Strauß, O.
Abstract:Changes in cell function occur by specific patterns of intracellular Ca(2+), activating Ca(2+)-sensitive proteins. The anoctamin (TMEM16) protein family has Ca(2+)-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca(2+)-dependent phosphatidyl-scramblase activity. Using amino acid sequence analysis combined with measurements of ion channel function, we clarified the so far unknown Ano4 function as Ca(2+)-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca(2+) activated conductance with weak selectivity of K(+) > Na(+) > Li(+). Endogenously expressed Ca(2+)-dependent cation channels in the retinal pigment epithelium were identified as Ano4 by KO mouse-derived primary RPE cells and siRNA against Ano4. Exchanging a negatively charged amino acid in the putative pore region (AA702-855) into a positive one (E775K) turns Ano4-elicited currents into Cl(-) currents evidencing its importance for ion selectivity. The molecular identification of Ano4 as a Ca(2+)-activated cation channel advances the understanding of its role in Ca(2+) signaling.
Keywords:Anoctamins, Calcium, Calcium Channels, Cations, HEK293 Cells, Knockout Mice, Animals, Mice
Source:Scientific Reports
Publisher:Nature Publishing Group
Page Range:2257
Date:19 February 2019
Official Publication:https://doi.org/10.1038/s41598-018-37287-y
PubMed:View item in PubMed

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