title: Differential requirements for retinal degeneration slow intermolecular disulfide-linked oligomerization in rods versus cones.
abstract: It is commonly assumed that the ultrastructural organization of the rim region of outer segment (OS) discs in rods and lamellae in cones requires functional retinal degeneration slow/rod outer segment membrane protein 1 (Rds/Rom-1) complexes. Cysteine-150 (C150) in Rds has been implicated in intermolecular disulfide bonding essential for functional Rds complexes. Transgenic mice containing the Rds C150S mutation (C150S-Rds) failed to form higher-order Rds oligomers, although interactions between C150S-Rds and Rom-1 occurred in rods, but not in cones. C150S-Rds mice exhibited marked early-onset reductions in cone function and abnormal OS structure. In contrast, C150S-Rds expression in rods partly rescued the rds(+/-) phenotype. Although C150S-Rds was detected in the OSs in rods and cones, a substantial percentage of C150S-Rds and cone opsins were mislocalized to different cellular compartments in cones. The results of this study provide novel insights into the importance of C150 in Rds oligomerization and the differences in Rds requirements in rods versus cones. The apparent OS structural differences between rods and cones may cause cones to be more susceptible to the elimination of higher-order Rds/Rom-1 oligomers (e.g. as mediated by mutation of the Rds C150 residue).
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Chakraborty
authors.forename: Xi-Qin
authors.initials: XQ
authors.lastname: Ding
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D004220:Disulfides / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D064531:Peripherins; D011485:Protein Binding; D021381:Protein Transport; D017949:Retinal Cone Photoreceptor Cells / Q000737:chemistry / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry / Q000378:metabolism*; D059470:Tetraspanins
chemical_list: D004220:Disulfides; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064531:Peripherins; C578996:Prph2 protein, mouse; C081477:Rom1 protein, mouse; D059470:Tetraspanins