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
| Autor: | Schmid, Verena, Wurzel, Alexander, Wetzel, Christian H., Plössl, Karolina, Bruckmann, Astrid, Luckner, Patricia, Weber, Bernhard H. F., Friedrich, Ulrike |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Pharmacology
Male Mammals ddc:610 Retinoschisis Swine X-linked juvenile retinoschisis · Retinoschisin · RS1 · Voltage-gated potassium channel · Kv2.1 · Kv8.2 · Retinal Na/K-ATPase 610 Medizin Cell Biology Cellular and Molecular Neuroscience Mice Potassium Molecular Medicine Animals 570 Biowissenschaften Biologie Photoreceptor Cells ddc:570 Sodium-Potassium-Exchanging ATPase Eye Proteins Molecular Biology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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