title: Retinal Degeneration Slow (RDS) Glycosylation Plays a Role in Cone Function and in the Regulation of RDS·ROM-1 Protein Complex Formation.
abstract: The photoreceptor-specific glycoprotein retinal degeneration slow (RDS, also called PRPH2) is necessary for the formation of rod and cone outer segments. Mutations in RDS cause rod and cone-dominant retinal disease, and it is well established that both cell types have different requirements for RDS. However, the molecular mechanisms for this difference remain unclear. Although RDS glycosylation is highly conserved, previous studies have revealed no apparent function for the glycan in rods. In light of the highly conserved nature of RDS glycosylation, we hypothesized that it is important for RDS function in cones and could underlie part of the differential requirement for RDS in the two photoreceptor subtypes. We generated a knockin mouse expressing RDS without the N-glycosylation site (N229S). Normal levels of RDS and the unglycosylated RDS binding partner rod outer segment membrane protein 1 (ROM-1) were found in N229S retinas. However, cone electroretinogram responses were decreased by 40% at 6 months of age. Because cones make up only 3-5% of photoreceptors in the wild-type background, N229S mice were crossed into the nrl(-/-) background (in which all rods are converted to cone-like cells) for biochemical analysis. In N229S/nrl(-/-) retinas, RDS and ROM-1 levels were decreased by ~60% each. These data suggest that glycosylation of RDS is required for RDS function or stability in cones, a difference that may be due to extracellular versus intradiscal localization of the RDS glycan in cones versus rods.
authors.affiliation: From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Stuck
authors.affiliation: From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.affiliation: From the Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104 mnaash@central.uh.edu.
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D006031:Glycosylation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D064531:Peripherins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000502:physiology; D059470:Tetraspanins
chemical_list: D005136:Eye Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D064531:Peripherins; C578996:Prph2 protein, mouse; C081477:Rom1 protein, mouse; D059470:Tetraspanins
keywords: N229S; glycosylation; oligomerization; peripherin-2; photoreceptor; retina; tetraspanin