TY  - JOUR
AU  - Reichhart, Nadine
AU  - Schöberl, Simon
AU  - Keckeis, Susanne
AU  - Alfaar, Ahmad S.
AU  - Roubeix, Christophe
AU  - Cordes, Magdalena
AU  - Crespo-Garcia, Sergio
AU  - Haeckel, Akvile
AU  - Kociok, Norbert
AU  - Föckler, Renate
AU  - Fels, Gabriele
AU  - Mataruga, Anja
AU  - Rauh, Robert
AU  - Milenkovic, Vladimir M.
AU  - Zühlke, Kerstin
AU  - Klussmann, Enno
AU  - Schellenberger, Eyk
AU  - Strauß, Olaf
TI  - Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel
JO  - Scientific reports
VL  - 9
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - FZJ-2019-01609
SP  - 2257
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30783137
UR  - <Go to ISI:>//WOS:000459092800027
DO  - DOI:10.1038/s41598-018-37287-y
UR  - https://juser.fz-juelich.de/record/860976
ER  -