Ploessl, Karolina and Royer, Melanie and Bernklau, Sarah and Tavraz, Neslihan N. and Friedrich, Thomas and Wild, Jens and Weber, Bernhard H. F. and Friedrich, Ulrike (2017) Retinoschisin is linked to retinal Na/K-ATPase signaling and localization. MOLECULAR BIOLOGY OF THE CELL, 28 (16). pp. 2178-2189. ISSN 1059-1524, 1939-4586
Full text not available from this repository. (Request a copy)Abstract
Mutations in the RS1 gene cause X-linked juvenile retinoschisis (XLRS), a hereditary retinal dystrophy. We recently showed that retinoschisin, the protein encoded by RS1, regulates ERK signaling and apoptosis in retinal cells. In this study, we explored an influence of retinoschisin on the functionality of the Na/K-ATPase, its interaction partner at retinal plasma membranes. We show that retinoschisin binding requires the beta 2-subunit of the Na/K-ATPase, whereas the alpha-subunit is exchangeable. Our investigations revealed no effect of retinoschisin on Na/K-ATPase-mediated ATP hydrolysis and ion transport. However, we identified an influence of retinoschisin on Na/K-ATPase-regulated signaling cascades and Na/K-ATPase localization. In addition to the known ERK deactivation, retinoschisin treatment of retinoschisin-deficient (Rs1h(-/Y)) murine retinal explants decreased activation of Src, an initial transmitter in Na/K-ATPase signal transduction, and of Ca2+ signaling marker Camk2. Immunohistochemistry on murine retinae revealed an overlap of the retinoschisin-Na/K-ATPase complex with proteins involved in Na/K-ATPase signaling, such as caveolin, phospholipase C, Src, and the IP3 receptor. Finally, retinoschisin treatment altered Na/K-ATPase localization in photoreceptors of Rs1h(-/Y) retinae. Taken together, our results suggest a regulatory effect of retinoschisin on Na/K-ATPase signaling and localization, whereas Na/K-ATPase-dysregulation caused by retinoschisin deficiency could represent an initial step in XLRS pathogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA+/K+-ATPASE; JUVENILE RETINOSCHISIS; SODIUM-PUMP; ANKYRIN-B; K-ATPASE; NA,K-ATPASE ACTIVITY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BIPOLAR CELLS; MAP KINASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 28 Feb 2019 10:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1475 |
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