title: The C terminus of peripherin/rds participates in rod outer segment targeting and alignment of disk incisures.
abstract: Protein targeting is essential for domain specialization in polarized cells. In photoreceptors, three distinct membrane domains exist in the outer segment: plasma membrane, disk lamella, and disk rim. Peripherin/retinal degeneration slow (rds) and rom-1 are photoreceptor-specific members of the transmembrane 4 superfamily of transmembrane proteins, which participate in disk morphogenesis and localize to rod outer segment (ROS) disk rims. We examined the role of their C termini in targeting by generating transgenic Xenopus laevis expressing green fluorescent protein (GFP) fusion proteins. A GFP fusion containing residues 317-336 of peripherin/rds localized uniformly to disk membranes. A longer fusion (residues 307-346) also localized to the ROS but exhibited higher affinity for disk rims than disk lamella. In contrast, the rom-1 C terminus did not promote ROS localization. The GFP-peripherin/rds fusion proteins did not immunoprecipitate with peripherin/rds or rom-1, suggesting this region does not form intermolecular interactions and is not involved in subunit assembly. Presence of GFP-peripherin/rds fusions correlated with disrupted incisures, disordered ROS tips, and membrane whorls. These abnormalities may reflect competition of the fusion proteins for other proteins that interact with peripherin/rds. This work describes novel roles for the C terminus of peripherin/rds in targeting and maintaining ROS structure and its potential involvement in inherited retinal degenerations.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. btam@interchange.ubc.ca
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Tam
authors.forename: Orson L
authors.initials: OL
authors.lastname: Moritz
authors.forename: David S
authors.initials: DS
authors.lastname: Papermaster
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002417:Cattle; D002455:Cell Division; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000737:chemistry*; D008164:Luminescent Proteins / Q000737:chemistry / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D064531:Peripherins; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species; D012374:Rod Cell Outer Segment / Q000378:metabolism*; D013997:Time Factors; D019076:Transgenes; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578995:PRPH protein, Xenopus; C578994:PRPH protein, human; C578997:PRPH2 protein, human; D064531:Peripherins; D017382:Reactive Oxygen Species; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins