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000860976 1001_ $$0P:(DE-HGF)0$$aReichhart, Nadine$$b0
000860976 245__ $$aAnoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel
000860976 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2019
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000860976 520__ $$aChanges 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.
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000860976 7001_ $$0P:(DE-HGF)0$$aSchöberl, Simon$$b1
000860976 7001_ $$0P:(DE-HGF)0$$aKeckeis, Susanne$$b2
000860976 7001_ $$00000-0002-0930-4583$$aAlfaar, Ahmad S.$$b3
000860976 7001_ $$0P:(DE-HGF)0$$aRoubeix, Christophe$$b4
000860976 7001_ $$0P:(DE-HGF)0$$aCordes, Magdalena$$b5
000860976 7001_ $$0P:(DE-HGF)0$$aCrespo-Garcia, Sergio$$b6
000860976 7001_ $$0P:(DE-HGF)0$$aHaeckel, Akvile$$b7
000860976 7001_ $$00000-0003-4898-6035$$aKociok, Norbert$$b8
000860976 7001_ $$0P:(DE-HGF)0$$aFöckler, Renate$$b9
000860976 7001_ $$0P:(DE-HGF)0$$aFels, Gabriele$$b10
000860976 7001_ $$0P:(DE-Juel1)133608$$aMataruga, Anja$$b11$$ufzj
000860976 7001_ $$00000-0002-9406-3939$$aRauh, Robert$$b12
000860976 7001_ $$0P:(DE-HGF)0$$aMilenkovic, Vladimir M.$$b13
000860976 7001_ $$0P:(DE-HGF)0$$aZühlke, Kerstin$$b14
000860976 7001_ $$00000-0003-4004-5003$$aKlussmann, Enno$$b15
000860976 7001_ $$0P:(DE-HGF)0$$aSchellenberger, Eyk$$b16
000860976 7001_ $$0P:(DE-HGF)0$$aStrauß, Olaf$$b17$$eCorresponding author
000860976 773__ $$0PERI:(DE-600)2615211-3$$a10.1038/s41598-018-37287-y$$gVol. 9, no. 1, p. 2257$$n1$$p2257$$tScientific reports$$v9$$x2045-2322$$y2019
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