Ousingsawat, Jiraporn and Wanitchakool, Podchanart and Schreiber, Rainer and Wuelling, Manuela and Vortkamp, Andrea and Kunzelmann, Karl (2015) Anoctamin-6 Controls Bone Mineralization by Activating the Calcium Transporter NCX1. JOURNAL OF BIOLOGICAL CHEMISTRY, 290 (10). pp. 6270-6280. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
Anoctamin-6 (Ano6, TMEM16F) belongs to a family of putative Ca2+-activated Cl- channels and operates as membrane phospholipid scramblase. Deletion of Ano6 leads to reduced skeleton size, skeletal deformities, and mineralization defects in mice. However, it remains entirely unclear how a lack of Ano6 leads to a delay in bone mineralization by osteoblasts. The Na+/Ca2+ exchanger NCX1 was found to interact with Ano6 in a two-hybrid split-ubiquitin screen. Using human osteoblasts and osteoblasts from Ano6(-/-) and WT mice, we demonstrate that NCX1 requires Ano6 to efficiently translocate Ca2+ out of osteoblasts into the calcifying bone matrix. Ca2+-activated anion currents are missing in primary osteoblasts isolated from Ano6 null mice. Our findings demonstrate the importance of NCX1 for bone mineralization and explain why deletion of an ion channel leads to the observed mineralization defect: Ano6 Cl- currents are probably required to operate as a Cl- bypass channel, thereby compensating net Na+ charge movement by NCX1.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA+/CA2+ EXCHANGER ISOFORMS; CA2+-ACTIVATED CL-CHANNELS; MEMBRANE CA2+ ATPASE; CHLORIDE CHANNEL; OSTEOBLASTS; PHOSPHATE; TMEM16F; OSTEOCLASTS; INHIBITION; EXPRESSION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jul 2019 07:31 |
| Last Modified: | 24 Jul 2019 07:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5800 |
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