Stress-kinase regulation of TASK-1 and TASK-3
Background/Aims: TASK channels belong to the two-pore-domain potassium (K2P) channel family. TASK-1 is discussed to contribute to chronic atrial fibrillation (AFib) and has been together with uncoupling protein 1 found as a marker protein of brown adipose tissue (BAT) fat. In addition, TASK-1 was li...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Cellular physiology and biochemistry
Year: 2017, Volume: 44, Issue: 3, Pages: 1024-1037 |
| ISSN: | 1421-9778 |
| DOI: | 10.1159/000485402 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1159/000485402 Verlag, kostenfrei, Volltext: https://www.karger.com/Article/FullText/485402 
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| Author Notes: | Susanne Rinné, Aytug K. Kiper, Constanze Schmidt, Beatriz Ortiz-Bonnin, Simone Zwiener, Guiscard Seebohm, Niels Decher |
| Summary: | Background/Aims: TASK channels belong to the two-pore-domain potassium (K2P) channel family. TASK-1 is discussed to contribute to chronic atrial fibrillation (AFib) and has been together with uncoupling protein 1 found as a marker protein of brown adipose tissue (BAT) fat. In addition, TASK-1 was linked in a genome-wide association study to an increased body mass index. A recent study showed that TASK-1 inhibition is causing obesity in mice by a BAT whitening and that these effects are linked to the mineralocorticoid receptor pathway, albeit the mechanism remained elusive. Therefore, we aimed to probe whether K2P channels are regulated by serum- and glucocorticoid-inducible kinases (SGKs) which are known to modify many cellular functions by modulating ion channels. Methods: To this end we used functional co-expression studies and chemiluminescence-assays in Xenopus oocytes, together with fluorescence imaging and quantitative PCR experiments. Results: SGKs and proteinkinase B (PKB) induced a strong, dose- and time-dependent current reduction of TASK-1 and TASK-3. SGK co-expression reduced the surface expression of TASK-1/3, leading to a predominant localization of the channels into late endosomes. The down regulation of TASK-3 channels was abrogated by the dynamin inhibitor dynasore, confirming a role of SGKs in TASK-1/3 channel endocytosis. Conclusion: Stress-mediated changes in SGK expression pattern or activation is likely to alter TASK-1/3 expression at the surface membrane. The observed TASK-1 regulation might contribute to the pathogenesis of chronic AFib and provide a mechanistic link between increased mineralocorticoid levels and TASK-1 reduction, both linked to BAT whitening. |
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| Item Description: | Published online: November 27, 2017 Gesehen am 27.06.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1421-9778 |
| DOI: | 10.1159/000485402 |