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. 1992 Feb 1;116(3):659–667. doi: 10.1083/jcb.116.3.659

Localization of peripherin/rds in the disk membranes of cone and rod photoreceptors: relationship to disk membrane morphogenesis and retinal degeneration

PMCID: PMC2289304  PMID: 1730772

Abstract

The outer segments of vertebrate rod photoreceptor cells consist of an ordered stack of membrane disks, which, except for a few nascent disks at the base of the outer segment, is surrounded by a separate plasma membrane. Previous studies indicate that the protein, peripherin or peripherin/rds, is localized along the rim of mature disks of rod outer segments. A mutation in the gene for this protein has been reported to be responsible for retinal degeneration in the rds mouse. In the present study, we have shown by immunogold labeling of rat and ground squirrel retinas that peripherin/rds is present in the disk rims of cone outer segments as well as rod outer segments. Additionally, in the basal regions of rod and cone outer segments, where disk morphogenesis occurs, we have found that the distribution of peripherin/rds is restricted to a region that is adjacent to the cilium. Extension of its distribution from the cilium coincides with the formation of the disk rim. These results support the model of disk membrane morphogenesis that predicts rim formation to be a second stage of growth, after the first stage in which the ciliary plasma membrane evaginates to form open nascent disks. The results also indicate how the proteins of the outer segment plasma membrane and the disk membranes are sorted into their separate domains: different sets of proteins may be incorporated into membrane outgrowths during different growth stages of disk morphogenesis. Finally, the presence of peripherin/rds protein in both cone and rod outer segment disks, together with the phenotype of the rds mouse, which is characterized by the failure of both rod and cone outer segment formation, suggest that the same rds gene is expressed in both types of photoreceptor cells.

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Selected References

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  1. Anderson D. H., Fisher S. K., Steinberg R. H. Mammalian cones: disc shedding, phagocytosis, and renewal. Invest Ophthalmol Vis Sci. 1978 Feb;17(2):117–133. [PubMed] [Google Scholar]
  2. Arikawa K., Williams D. S. Organization of actin filaments and immunocolocalization of alpha-actinin in the connecting cilium of rat photoreceptors. J Comp Neurol. 1989 Oct 22;288(4):640–646. doi: 10.1002/cne.902880410. [DOI] [PubMed] [Google Scholar]
  3. Begy C., Bridges C. D. Nucleotide and predicted protein sequence of rat retinal degeneration slow (rds). Nucleic Acids Res. 1990 May 25;18(10):3058–3058. doi: 10.1093/nar/18.10.3058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. COHEN A. I. The fine structure of the extrafoveal receptors of the Rhesus monkey. Exp Eye Res. 1961 Dec;1:128–136. doi: 10.1016/s0014-4835(61)80018-3. [DOI] [PubMed] [Google Scholar]
  5. Cohen A. I. New evidence supporting the linkage to extracellular space of outer segment saccules of frog cones but not rods. J Cell Biol. 1968 May;37(2):424–444. doi: 10.1083/jcb.37.2.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen A. I. Some cytological and initial biochemical observations on photoreceptors in retinas of rds mice. Invest Ophthalmol Vis Sci. 1983 Jul;24(7):832–843. [PubMed] [Google Scholar]
  7. Connell G. J., Molday R. S. Molecular cloning, primary structure, and orientation of the vertebrate photoreceptor cell protein peripherin in the rod outer segment disk membrane. Biochemistry. 1990 May 15;29(19):4691–4698. doi: 10.1021/bi00471a025. [DOI] [PubMed] [Google Scholar]
  8. Connell G., Bascom R., Molday L., Reid D., McInnes R. R., Molday R. S. Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):723–726. doi: 10.1073/pnas.88.3.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cook N. J., Molday L. L., Reid D., Kaupp U. B., Molday R. S. The cGMP-gated channel of bovine rod photoreceptors is localized exclusively in the plasma membrane. J Biol Chem. 1989 Apr 25;264(12):6996–6999. [PubMed] [Google Scholar]
  10. Corless J. M., Fetter R. D. Structural features of the terminal loop region of frog retinal rod outer segment disk membranes: III. Implications of the terminal loop complex for disk morphogenesis, membrane fusion, and cell surface interactions. J Comp Neurol. 1987 Mar 1;257(1):24–38. doi: 10.1002/cne.902570104. [DOI] [PubMed] [Google Scholar]
  11. Farrar G. J., Kenna P., Jordan S. A., Kumar-Singh R., Humphries M. M., Sharp E. M., Sheils D. M., Humphries P. A three-base-pair deletion in the peripherin-RDS gene in one form of retinitis pigmentosa. Nature. 1991 Dec 12;354(6353):478–480. doi: 10.1038/354478a0. [DOI] [PubMed] [Google Scholar]
  12. Hicks D., Molday R. S. Differential immunogold-dextran labeling of bovine and frog rod and cone cells using monoclonal antibodies against bovine rhodopsin. Exp Eye Res. 1986 Jan;42(1):55–71. doi: 10.1016/0014-4835(86)90017-5. [DOI] [PubMed] [Google Scholar]
  13. Hsu S. C., Molday R. S. Glyceraldehyde-3-phosphate dehydrogenase is a major protein associated with the plasma membrane of retinal photoreceptor outer segments. J Biol Chem. 1990 Aug 5;265(22):13308–13313. [PubMed] [Google Scholar]
  14. Jacobs G. H., Fisher S. K., Anderson D. H., Silverman M. S. Scotopic and photopic vision in the California ground squirrel: physiological and anatomical evidence. J Comp Neurol. 1976 Jan 15;165(2):209–227. doi: 10.1002/cne.901650207. [DOI] [PubMed] [Google Scholar]
  15. Jansen H. G., Sanyal S. Development and degeneration of retina in rds mutant mice: electron microscopy. J Comp Neurol. 1984 Mar 20;224(1):71–84. doi: 10.1002/cne.902240107. [DOI] [PubMed] [Google Scholar]
  16. Johnson L. V., Blanks J. C. Application of acrylamide as an embedding medium in studies of lectin and antibody binding in the vertebrate retina. Curr Eye Res. 1984 Jul;3(7):969–974. doi: 10.3109/02713688409167215. [DOI] [PubMed] [Google Scholar]
  17. Kajiwara K., Hahn L. B., Mukai S., Travis G. H., Berson E. L., Dryja T. P. Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature. 1991 Dec 12;354(6353):480–483. doi: 10.1038/354480a0. [DOI] [PubMed] [Google Scholar]
  18. Kamps K. M., De Grip W. J., Daemen F. J. Use of a density modification technique for isolation of the plasma membrane of rod outer segments. Biochim Biophys Acta. 1982 May 7;687(2):296–302. doi: 10.1016/0005-2736(82)90558-2. [DOI] [PubMed] [Google Scholar]
  19. MacKenzie D., Molday R. S. Organization of rhodopsin and a high molecular weight glycoprotein in rod photoreceptor disc membranes using monoclonal antibodies. J Biol Chem. 1982 Jun 25;257(12):7100–7105. [PubMed] [Google Scholar]
  20. Molday R. S., Hicks D., Molday L. Peripherin. A rim-specific membrane protein of rod outer segment discs. Invest Ophthalmol Vis Sci. 1987 Jan;28(1):50–61. [PubMed] [Google Scholar]
  21. Molday R. S., Molday L. L. Differences in the protein composition of bovine retinal rod outer segment disk and plasma membranes isolated by a ricin-gold-dextran density perturbation method. J Cell Biol. 1987 Dec;105(6 Pt 1):2589–2601. doi: 10.1083/jcb.105.6.2589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. NILSSON S. E. RECEPTOR CELL OUTER SEGMENT DEVELOPMENT AND ULTRASTRUCTURE OF THE DISK MEMBRANES IN THE RETINA OF THE TADPOLE (RANA PIPIENS). J Ultrastruct Res. 1964 Dec;11:581–602. doi: 10.1016/s0022-5320(64)80084-8. [DOI] [PubMed] [Google Scholar]
  23. Nir I., Agarwal N., Papermaster D. S. Opsin gene expression during early and late phases of retinal degeneration in rds mice. Exp Eye Res. 1990 Sep;51(3):257–267. doi: 10.1016/0014-4835(90)90022-m. [DOI] [PubMed] [Google Scholar]
  24. Papermaster D. S., Reilly P., Schneider B. G. Cone lamellae and red and green rod outer segment disks contain a large intrinsic membrane protein on their margins: an ultrastructural immunocytochemical study of frog retinas. Vision Res. 1982;22(12):1417–1428. doi: 10.1016/0042-6989(82)90204-8. [DOI] [PubMed] [Google Scholar]
  25. Papermaster D. S., Schneider B. G., Zorn M. A., Kraehenbuhl J. P. Immunocytochemical localization of a large intrinsic membrane protein to the incisures and margins of frog rod outer segment disks. J Cell Biol. 1978 Aug;78(2):415–425. doi: 10.1083/jcb.78.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pedler C. M., Tilly R. The fine structure of photoreceptor discs. Vision Res. 1967 Nov;7(11):829–836. doi: 10.1016/0042-6989(67)90003-x. [DOI] [PubMed] [Google Scholar]
  27. Reid D. M., Friedel U., Molday R. S., Cook N. J. Identification of the sodium-calcium exchanger as the major ricin-binding glycoprotein of bovine rod outer segments and its localization to the plasma membrane. Biochemistry. 1990 Feb 13;29(6):1601–1607. doi: 10.1021/bi00458a035. [DOI] [PubMed] [Google Scholar]
  28. Sanyal S., Jansen H. G. Absence of receptor outer segments in the retina of rds mutant mice. Neurosci Lett. 1981 Jan 1;21(1):23–26. doi: 10.1016/0304-3940(81)90051-3. [DOI] [PubMed] [Google Scholar]
  29. Steinberg R. H., Fisher S. K., Anderson D. H. Disc morphogenesis in vertebrate photoreceptors. J Comp Neurol. 1980 Apr 1;190(3):501–508. doi: 10.1002/cne.901900307. [DOI] [PubMed] [Google Scholar]
  30. Travis G. H., Brennan M. B., Danielson P. E., Kozak C. A., Sutcliffe J. G. Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature. 1989 Mar 2;338(6210):70–73. doi: 10.1038/338070a0. [DOI] [PubMed] [Google Scholar]
  31. Travis G. H., Christerson L., Danielson P. E., Klisak I., Sparkes R. S., Hahn L. B., Dryja T. P., Sutcliffe J. G. The human retinal degeneration slow (RDS) gene: chromosome assignment and structure of the mRNA. Genomics. 1991 Jul;10(3):733–739. doi: 10.1016/0888-7543(91)90457-p. [DOI] [PubMed] [Google Scholar]
  32. Travis G. H., Sutcliffe J. G., Bok D. The retinal degeneration slow (rds) gene product is a photoreceptor disc membrane-associated glycoprotein. Neuron. 1991 Jan;6(1):61–70. doi: 10.1016/0896-6273(91)90122-g. [DOI] [PubMed] [Google Scholar]
  33. Vaughan D. K., Fisher S. K. Cytochalasin D disrupts outer segment disc morphogenesis in situ in rabbit retina. Invest Ophthalmol Vis Sci. 1989 Feb;30(2):339–342. [PubMed] [Google Scholar]
  34. Williams D. S., Linberg K. A., Vaughan D. K., Fariss R. N., Fisher S. K. Disruption of microfilament organization and deregulation of disk membrane morphogenesis by cytochalasin D in rod and cone photoreceptors. J Comp Neurol. 1988 Jun 8;272(2):161–176. doi: 10.1002/cne.902720202. [DOI] [PubMed] [Google Scholar]

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