{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T15:09:46Z","timestamp":1775488186117,"version":"3.50.1"},"reference-count":76,"publisher":"American Society for Cell Biology (ASCB)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>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 \u03b22-subunit of the Na\/K-ATPase, whereas the \u03b1-subunit is exchangeable. Our investigations revealed no effect of retinoschisin on Na\/K-ATPase\u2013mediated ATP hydrolysis and ion transport. However, we identified an influence of retinoschisin on Na\/K-ATPase\u2013regulated signaling cascades and Na\/K-ATPase localization. In addition to the known ERK deactivation, retinoschisin treatment of retinoschisin-deficient (Rs1h<jats:sup>-\/Y<\/jats:sup>) murine retinal explants decreased activation of Src, an initial transmitter in Na\/K-ATPase signal transduction, and of Ca<jats:sup>2+<\/jats:sup>signaling marker Camk2. Immunohistochemistry on murine retinae revealed an overlap of the retinoschisin\u2013Na\/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<jats:sup>-\/Y<\/jats:sup>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.<\/jats:p>","DOI":"10.1091\/mbc.e17-01-0064","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T00:50:18Z","timestamp":1497487818000},"page":"2178-2189","source":"Crossref","is-referenced-by-count":36,"title":["Retinoschisin is linked to retinal Na\/K-ATPase signaling and localization"],"prefix":"10.1091","volume":"28","author":[{"given":"Karolina","family":"Pl\u00f6ssl","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Royer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Bernklau","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neslihan N.","family":"Tavraz","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technical University of Berlin, 10623 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technical University of Berlin, 10623 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Wild","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital of Regensburg, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard H. 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