Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel

Reichhart N, Schoeberl S, Keckeis S, Alfaar AS, Roubeix C, Cordes M, Crespo-Garcia S, Haeckel A, Kociok N, Foeckler R, Fels G, Mataruga A, Rauh R, Milenkovic VM, Zuehlke K, Klussmann E, Schellenberger E, Strauss O (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 9

DOI: 10.1038/s41598-018-37287-y

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.

Authors with CRIS profile

Robert Rauh Medizinische Fakultät

Additional Organisation(s)

Institut für Zelluläre und Molekulare Physiologie

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universität Regensburg DE Germany (DE) Freie Universität Berlin DE Germany (DE) Forschungszentrum Jülich / Research Centre Jülich (FZJ) DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE)

How to cite

APA:

Reichhart, N., Schoeberl, S., Keckeis, S., Alfaar, A.S., Roubeix, C., Cordes, M.,... Strauss, O. (2019). Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel. Scientific Reports, 9. https://dx.doi.org/10.1038/s41598-018-37287-y

MLA:

Reichhart, Nadine, et al. "Anoctamin-4 is a bona fide Ca2+-dependent non-selective cation channel." Scientific Reports 9 (2019).

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