Retinoschisin is linked to retinal Na/K-ATPase signaling and localization

Author:

Plössl Karolina1,Royer Melanie1,Bernklau Sarah1,Tavraz Neslihan N.2,Friedrich Thomas2,Wild Jens3,Weber Bernhard H. F.1,Friedrich Ulrike1

Affiliation:

1. Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany

2. Institute of Chemistry, Technical University of Berlin, 10623 Berlin, Germany

3. Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany

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 β2-subunit of the Na/K-ATPase, whereas the α-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-/Yretinae. 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.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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