Schmid, Verena and Wurzel, Alexander and Wetzel, Christian H. and Ploessl, Karolina and Bruckmann, Astrid and Luckner, Patricia and Weber, Bernhard H. F. and Friedrich, Ulrike (2022) Retinoschisin and novel Na/K-ATPase interaction partners Kv2.1 and Kv8.2 define a growing protein complex at the inner segments of mammalian photoreceptors. CELLULAR AND MOLECULAR LIFE SCIENCES, 79 (8): 448. ISSN 1420-682X, 1420-9071
Full text not available from this repository. (Request a copy)Abstract
The RS1 gene on Xp 22.13 encodes retinoschisin which is known to directly interact with the retinal Na/K-ATPase at the photoreceptor inner segments. Pathologic mutations in RS1 cause X-linked juvenile retinoschisis (XLRS), a hereditary retinal dystrophy in young males. To further delineate the retinoschisin-Na/K-ATPase complex, co-immunoprecipitation was performed with porcine and murine retinal lysates targeting the ATP1A3 subunit. This identified the voltage-gated potassium (Kv) channel subunits Kv2.1 and Kv8.2 as direct interaction partners of the retinal Na/K-ATPase. Colocalization of the individual components of the complex was demonstrated at the membrane of photoreceptor inner segments. We further show that retinoschisin-deficiency, a frequent consequence of molecular pathology in XLRS, causes mislocalization of the macromolecular complex during postnatal retinal development with a simultaneous reduction of Kv2.1 and Kv8.2 protein expression, while the level of retinal Na/K-ATPase expression remains unaffected. Patch-clamp analysis revealed no effect of retinoschisin-deficiency on Kv channel mediated potassium ion currents in vitro. Together, our data suggest that Kv2.1 and Kv8.2 together with retinoschisin and the retinal Na/K-ATPase are integral parts of a macromolecular complex at the photoreceptor inner segments. Defective compartmentalization of this complex due to retinoschisin-deficiency may be a crucial step in initial XLRS pathogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | X-LINKED RETINOSCHISIS; CONE DYSTROPHY; NA+/K+-ATPASE; CELL-DEATH; GENE; EXPRESSION; RS1; SRC; IDENTIFICATION; STOICHIOMETRY; X-linked juvenile retinoschisis; Retinoschisin; RS1; Voltage-gated potassium channel; Kv2; 1; Kv8; 2; Retinal Na; K-ATPase |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Psychiatrie und Psychotherapie Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Nov 2023 14:17 |
| Last Modified: | 27 Nov 2023 14:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56847 |
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