%0 Journal Article
%A Reichhart, Nadine
%A Schöberl, Simon
%A Keckeis, Susanne
%A Alfaar, Ahmad S.
%A Roubeix, Christophe
%A Cordes, Magdalena
%A Crespo-Garcia, Sergio
%A Haeckel, Akvile
%A Kociok, Norbert
%A Föckler, Renate
%A Fels, Gabriele
%A Mataruga, Anja
%A Rauh, Robert
%A Milenkovic, Vladimir M.
%A Zühlke, Kerstin
%A Klussmann, Enno
%A Schellenberger, Eyk
%A Strauß, Olaf
%T Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel
%J Scientific reports
%V 9
%N 1
%@ 2045-2322
%C [London]
%I Macmillan Publishers Limited, part of Springer Nature
%M FZJ-2019-01609
%P 2257
%D 2019
%X Changes in cell function occur by specific patterns of intracellular Ca2+, activating Ca2+-sensitive proteins. The anoctamin (TMEM16) protein family has Ca2+-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca2+-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 Ca2+-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca2+ activated conductance with weak selectivity of K+ > Na+ > Li+. Endogenously expressed Ca2+-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 Ca2+-activated cation channel advances the understanding of its role in Ca2+ signaling.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30783137
%U <Go to ISI:>//WOS:000459092800027
%R 10.1038/s41598-018-37287-y
%U https://juser.fz-juelich.de/record/860976