Disrupted Plasma Membrane Protein Homeostasis in a <i>Xenopus Laevis</i> Model of Retinitis Pigmentosa

Abstract

Retinal ciliopathy is the most common form of inherited blinding disorder frequently manifesting rhodopsin mislocalization. Our understanding of the relationships between rhodopsin mislocalization and photoreceptor dysfunction/degeneration has been far from complete. This study uncovers a hitherto uncharacterized consequence of rhodopsin mislocalization: the activation of the lysosomal pathway, which negatively regulates the amount of the sodium-potassium ATPase (NKAα) on the inner segment plasma membrane. On the plasma membrane, mislocalized rhodopsin extracts NKAα and sends it to lysosomes where they are co-degraded. Compromised NKAα function leads to shortening and loss of the photoreceptor outer segments as observed for various inherited blinding disorders. In summary, this study revealed a novel pathogenic mechanism applicable to various forms of blinding disorders caused by rhodopsin mislocalization.