Role of Subunit Assembly in Autosomal Dominant Retinitis Pigmentosa Linked to Mutations in Peripherin 2

摘要: Peripherin 2 is a photoreceptor-specific membrane protein implicated in outer segment disk morphogenesis and linked to various retinopathies including autosomal dominant retinitis pigmentosa (ADRP). ROM1 assemble as mixture of core noncovalent homomeric heteromeric tetramers that further link together through disulfide bonds form higher order oligomers. These complexes are critical for rim formation structure interaction with the cGMP-gated channel other photoreceptor proteins. We have examined role subunit assembly peripherin targeting disks, structure, degeneration by examining molecular cellular properties mutants COS-1 cells transgenic Xenopus laevis rod photoreceptors. Wild-type (WT) ADRP-linked P216L mutant were transported incorporated into newly formed disks X. laevis. The mutant, however, induced progressive instability possibly introduction new N-linked oligosaccharide chain. In contrast, C214S L185P disease-linked, tetramerization-defective mutants, retained inner segment, but did not affect or induce degeneration. Together, these results indicate mutations can cause ADRP either deficiency WT (C214S, 1.185P) negative effect on stability (P216L).