The cat RDS transcript: candidate gene analysis and phylogenetic sequence analysis

Gorin, Michael B.; Snyder, Steven M.; Narfström, Kristina; Curtis, R.

doi:10.1007/bf00364792

Cited by 17 publications

(5 citation statements)

References 20 publications

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“…Figure 1 depicts the current topological model for peripherin/rds (1, 2) in the outer segment disc membrane and highlights the position and conservation of the 13 cysteine residues present in the bovine sequence. Residues shaded in black are absolutely conserved in both peripherin/rds and its homologous subunit, rom-1, across all species examined to date (2,3,8,(25)(26)(27)(28)(29)(30)(31). These seven conserved cysteines are confined to the large intradiscal L3-4 loop the third and fourth transmembrane segments.…”

Section: Resultsmentioning

confidence: 99%

Cysteine Residues of Photoreceptor Peripherin/rds: Role in Subunit Assembly and Autosomal Dominant Retinitis Pigmentosa

1998

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Peripherin/rds is a tetraspanning membrane glycoprotein that is essential for the morphogenesis and stabilization of outer segments of vertebrate rod and cone photoreceptor cells. Mutations in the gene for peripherin/rds are responsible for retinal degeneration in the rds mouse and a variety of progressive human retinal degenerative diseases including autosomal dominant retinitis pigmentosa and macular dystrophy. Peripherin/rds associates with rom-1, a homologous subunit, to form a heterotetrameric complex. This study examines the importance of cysteine residues for the structure of peripherin/rds and its assembly with rom-1. Each of the 13 cysteine residues in bovine peripherin/rds was individually replaced with a serine residue by site-directed mutagenesis, and the resulting mutants were expressed individually or together with rom-1 in COS-1 cells. SDS-polyacrylamide gel electrophoresis, immunoprecipitation, and velocity sedimentation were carried out to evaluate the ability of these mutants to form disulfide-linked homodimers, associate with rom-1, and assemble into tetramers characteristic of wild-type peripherin/rds. Substitution of each of the six nonconserved cysteines had no apparent effect on dimer formation, folding, or subunit assembly. In contrast, replacement of any of the seven conserved cysteine residues predicted to lie within a 150 amino acid intradiscal loop significantly altered these properties. Six of these mutants, including a C214S mutant linked to autosomal dominant retinitis pigmentosa, were unable to fold normally, interact with rom-1, or self-assemble into tetramers but instead formed a mixture of large aggregates and a smaller component, most likely a dimer. The C150S mutant, on the other hand, was incapable of forming intermolecular disulfide bonds but did associate with rom-1 into a heterotetramer. These results suggest that (1) the conserved C150 residue is required for intermolecular disulfide bonding but not subunit assembly; (2) the six other conserved cysteine residues are crucial for proper folding and subunit assembly, possibly through formation of intramolecular disulfide bonds; and (3) the misfolding and defective subunit assembly of the C214S mutant is responsible for a form of monogenic autosomal dominant retinitis pigmentosa.

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Section: Resultsmentioning

confidence: 99%

Cysteine Residues of Photoreceptor Peripherin/rds: Role in Subunit Assembly and Autosomal Dominant Retinitis Pigmentosa

1998

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“…Function-In addition to the murine and bovine molecules originally described, homology cloning has identified roughly a dozen peripherin/rds orthologs in fish, amphibians, birds, and mammals (Begy and Bridges, 1990;Connell and Molday, 1990;Travis et al, 1989;1991a,b;Gorin et al, 1993;Moghrabi et al, 1995;Kedzierski et al, 1996;Weng et al, 1998). They are highly conserved at the amino acid level (50-90% similarity) and share several distinctive features, shown schematically in Figure 5.…”

Section: Molecular Genetics Offers Clues To Key Features Of Protein Smentioning

confidence: 99%

Photoreceptor renewal: A role for peripherin/rds

Boesze‐Battaglia¹,

Goldberg²

2002

International Review of Cytology

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Visual transduction begins with the detection of light within the photoreceptor cell layer of the retina. Within this layer, specialized cells, termed rods and cones, contain the proteins responsible for light capture and its transduction to nerve impulses. The phototransductive proteins reside within an outer segment region that is connected to an inner segment by a thin stalk rich in cytoskeletal elements. A unique property of the outer segments is the presence of an elaborate intracellular membrane system that holds the phototransduction proteins and provides the requisite lipid environment. The maintenance of normal physiological function requires that these postmitotic cells retain the unique structure of the outer segment regions-stacks of membrane saccules in the case of rods and a continuous infolding of membrane in the case of cones. Both photoreceptor rod and cone cells achieve this through a series of coordinated steps. As new membranous material is synthesized, transported, and incorporated into newly forming outer segment membranes, a compensatory shedding of older membranous material occurs, thereby maintaining the segment at a constant length. These processes are collectively referred to as ROS (rod outer segment) or COS (cone outer segment) renewal. We review the cellular and molecular events responsible for these renewal processes and present the recent but compelling evidence, drawn from molecular genetic, biochemical, and biophysical approaches, pointing to an essential role for a unique tetraspanning membrane protein, called peripherin/rds, in the processes of disk morphogenesis.

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“…These observations imply that rom1, at least in part, is superfluous to the formation and maintenance of outer segments. Homologues of rds have been cloned from multiple species, including the human (Travis et al, 1991 a ), cow (Connell et al, 1991), dog (Moghrabi et al, 1995), rat (Begy and Bridges, 1990), cat (Gorin et al, 1993), Xenopus (Kedzierski et al, 1996), skate (Li et al, 1997), and chicken (Weng et al, 1998). A predicted motif conserved in all homologues of rds/peripherin is the site for N‐linked glycosylation at asparagine 229.…”

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confidence: 99%

Transgenic Analysis of Rds/Peripherin N‐Glycosylation

Kędzierski

Bok

Travis

1999

Journal of Neurochemistry

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Rds/peripherin is an integral membrane glycoprotein that is present in the rims of photoreceptor outer segment disks. In mammals, it is thought to stabilize the disk rim through heterophilic interactions with the related nonglycosylated protein rom1. Glycosylation of rds/peripherin at asparagine 229 is widely conserved in vertebrates. In this study, we investigated the role of rds/peripherin N-glycosylation. We generated transgenic mice that expressed only S231A-substituted rds/peripherin in their retinas. This protein was not glycosylated but formed covalent dimers with itself and with glycosylated rds/peripherin. Nonglycosylated rds/peripherin also interacted noncovalently with rom1 homodimers to form a heterooligomeric complex. The glycosylated rds/peripherin ⅐ ⅐ rom1 complex bound to concanavalin A-Sepharose, suggesting that the glycan is not directly involved in the interaction between these proteins. In double transgenic mice expressing normal and S231A-substituted rds/peripherin, the mRNA-toprotein ratios were similar for both transgenes, indicating no effect of N-glycosylation on rds/peripherin stability. Finally, expression of nonglycosylated rds/peripherin in transgenic mice rescued the phenotype of outer segment nondevelopment in retinal degeneration slow (rdsϪ/Ϫ) null mutants. These observations indicate that N-glycosylation of rds/peripherin is not required for its normal processing, stability, or in vivo function.

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The cat RDS transcript: candidate gene analysis and phylogenetic sequence analysis

Cited by 17 publications

References 20 publications

Cysteine Residues of Photoreceptor Peripherin/rds: Role in Subunit Assembly and Autosomal Dominant Retinitis Pigmentosa

Cysteine Residues of Photoreceptor Peripherin/rds: Role in Subunit Assembly and Autosomal Dominant Retinitis Pigmentosa

Photoreceptor renewal: A role for peripherin/rds

Transgenic Analysis of Rds/Peripherin N‐Glycosylation

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