Reichhart, Nadine and Schoeberl, Simon and Keckeis, Susanne and Alfaar, Ahmad S. and Roubeix, Christophe and Cordes, Magdalena and Crespo-Garcia, Sergio and Haeckel, Akvile and Kociok, Norbert and Foeckler, Renate and Fels, Gabriele and Mataruga, Anja and Rauh, Robert and Milenkovic, Vladimir M. and Zuehlke, Kerstin and Klussmann, Enno and Schellenberger, Eyk and Strauss, Olaf (2019) Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel. SCIENTIFIC REPORTS, 9: 2257. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED CL-CHANNEL; INDEPENDENT ACTIVATION; CALCIUM; EXPRESSION; TMEM16A; PROTEIN; FAMILY; PORES; FORMS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Medicine > Lehrstuhl für Psychiatrie und Psychotherapie > Molekulare Neurowissenscahften |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2020 06:57 |
| Last Modified: | 17 Apr 2020 06:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27531 |
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