The Role of Dominant Rhodopsin Mutations in Drosophila Retinal Degeneration

  • Phani Kurada
  • Timothy D. Tonini
  • Joseph E. O’Tousa


Mutations within the human rod opsin gene are responsible for approximately 25% of the autosomal dominant forms of retinitis pigmentosa (ADRP) afflicting human populations (l).There are over 60 different mutations known in the rhodopsin gene that cause ADRP. To account for the mechanisms by which these mutations can cause retinal degeneration, three general types of models have been considered. First, improper folding mutant protein may prevent its proper maturation (2). A second model is that the mutated forms may produce rhodopsins that are constitutively active, leading to increased metabolic activity (3). A third possibility is that the mutant proteins show improper cellular localization (4). All three views are consistent with a scenario by which the dominant rhodopsin mutation reduces the health of the photoreceptor, eventually causing the cell to degenerate. Understanding the molecular basis of rhodopsin-based forms of ADRP represents a major advance, but it is likely that successful strategies for alleviating the disease will require additional knowledge on the mechanisms by which these rhodopsin mutants trigger retinal degeneration.


Retinitis Pigmentosa Photoreceptor Cell Endoplasmic Reticulum Membrane Retinal Degeneration Photoreceptor Degeneration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Dryja, T. P., T. L. Mcgee, L. B. Hahn, G. S. Cowley, J. E. Olsson, E. Reichel, M. A. Sandberg and E. L. Berson, 1990, Mutations within the rhodopsin gene in patients with autosomal dominant retinitis-pigmentosa, New England J. Medicine. 323: 1302–1307.CrossRefGoogle Scholar
  2. 2.
    Sung, C.-H., C. M. Davenport and J. Nathans, 1993, Rhodopsin mutants responsible for autosomal dominant retinitis pigmentosa, J. Biol. Chem. 268: 26645–26649.PubMedGoogle Scholar
  3. 3.
    Robinson, P. R., G. B. Cohen, E. A. Zhukovsky and D. D. Oprian, 1992, Constitutively active mutants of rhodopsin, Neuron. 9: 719–725.PubMedCrossRefGoogle Scholar
  4. 4.
    Sung, C.-H., C. Makino, D. A. Baylor and J. Nathans, 1994, A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa result in a protein that is defective in localization to the photoreceptor outer segment, J. Neurosci. 14: 5818–5833.PubMedGoogle Scholar
  5. 5.
    Hotta, Y. and S. Benzer, 1969, Abnormal electroretinogram in visual mutants in Drosophila, Nature. 222: 354–356.PubMedCrossRefGoogle Scholar
  6. 6.
    Pak, W. L., J. J. Grossfield and N.V. White, 1969, Nonphototactic mutants in a study of vision of Drosophila, Nature. 222: 351–354.PubMedCrossRefGoogle Scholar
  7. 7.
    Pak, W. L. “ Mutations affecting the vision of Drosophila melanogaster.” Handbook of Genetics. King ed. 1976 Plenum. New York.Google Scholar
  8. 8.
    Stephenson, R. S., J. O’Tousa, N. J. Scavarda, L. L. Randall and W. L. Pak. “ Drosophila mutants with reduced rhodopsin content.” The Biology of Photoreception. Cosens and Vince-Price ed. 1983 Cambridge University Press Cambridge.Google Scholar
  9. 9.
    Stark, W. S. and W. G. Zitzmann, 1976, Isolation of adaptation mechanisms and photopigment spectra by vitamin A deprivation in Drosophila, J. Comp. Physiol 105: 15–27.CrossRefGoogle Scholar
  10. 10.
    Schinz, R. H., M.-V. C. Lo, D. C. Larrivee and W. L. Pak, 1982, Freeze-fracture study of the Drosophila photoreceptor membrane: mutations affecting membrane particle density, J. Cell Biol. 93: 961–969.PubMedCrossRefGoogle Scholar
  11. 11.
    Scavarda, N. J., J. O’Tousa and W. L. Pak, 1983, Drosophila locus with gene dosage effect on rhodopsin., Proc. Natl Acad. Sci. 80: 4441–4445.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    O’Tousa, J. E., W. Baehr, R. L. Martin, J. Hirsh, W. L. Pak and M. L. Applebury, 1985, The Drosophila ninaE gene encodes an opsin., Cell. 40: 839–850.PubMedCrossRefGoogle Scholar
  13. 13.
    Zuker, C. S., A. F. Cowman and G. M. Rubin, 1985, Isolation and structure of a rhodopsin gene from D. melanogaster, Cell. 40: 851–858.PubMedCrossRefGoogle Scholar
  14. 14.
    Koenig, J. and J. Merriam, 1977, Autosomal ERG mutants, Drosophila Information Service. 52: 50–51.Google Scholar
  15. 15.
    O’Tousa, J. E., D. S. Leonard and W. L. Pak, 1989, Morphological defects in ora JK84 photoreceptors caused by mutation in R1-6 opsin gene of Drosophila., J. Neurogenetics. 6: 41–52.CrossRefGoogle Scholar
  16. 16.
    Washburn, T. and J. E. O’Tousa, 1989, Molecular defects in Drosophila rhodopsin mutants, J. Biol. Chem. 264: 15464–15466.PubMedGoogle Scholar
  17. 17.
    Blest, A. D., S. Stowe and W. Eddey, 1982, A labile, Ca+2-dependent cytoskeleton in rhabdomeral microvilli of blowflies, Cell Tissue Res. 223: 553–573.PubMedCrossRefGoogle Scholar
  18. 18.
    Stark, W. S. and S. D. Carlson, 1983, Ultrastructure of the compound eye and the first optic neuropile of the photoreceptor mutant ora JK84 of Drosophila, Cell Tiss. Res. 233: 305–317.CrossRefGoogle Scholar
  19. 19.
    Stark, W. S. and R. Sapp, 1987, Ultrastructure of the retina of Drosophila melanogaster. the mutant ora (outer rhabdomeres absent) and its inhibition of degeneration in rdgB (retinal degeneration-B), J. Neurogenet. 4: 227–240.PubMedGoogle Scholar
  20. 20.
    Johnson, E. C. and W. L. Pak, 1986, Electrophysiological study of Drosophila rhodopsin mutants, J. Gen. Physiol. 88: 651–673.PubMedCrossRefGoogle Scholar
  21. 21.
    Leonard, D. S., V. D. Bowman, D. F. Ready and W. L. Pak, 1992, Photoreceptor degeneration associated with mutations in presumptive opsin structural gene of Drosophila, J. Neurobiology. 23: 605–626.CrossRefGoogle Scholar
  22. 22.
    Kurada, P. and J. E. O’Tousa, 1995, Retinal degeneration caused by dominant rhodopsin mutants in Drosophila., Neuron. 14 (in press).Google Scholar
  23. 23.
    Colley, N. J., J. A. Casill, E. K. Baker and C. S. Zuker, 1995, Defective intracellular transport is the molecular basis of rhodopsin-dependent dominant retinal degeneration, Proc. Natl. Acad. Sci. USA. 92: 3070–3074.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Steele, F., W. T., R. Rieger and J. E. O’Tousa, 1992, Drosophila rdgC encodes a novel protein phosphatase, Cell. 69: 669–676.PubMedCrossRefGoogle Scholar
  25. 25.
    Byk, T., M. Bar-Yaacov, Y. N. Doza, B. Minke and Z. Selinger, 1993, Regulatory arrestin cycle secures the fidelity and maintenance of the fly photoreceptor cell, Proc. Natl. Acad. Sci. USA. 90: 1907–1911.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Meyertholen, E. P., P. J. Stein, M. A. Williams and S. E. Ostroy, 1987, Studies of the Drosophila norpA phototransduction mutant II. Photoreceptor degeneration and rhodopsin maintenance, J. Comp. Physiol. 161: 793–798.CrossRefGoogle Scholar
  27. 27.
    Stark, W. S., R. Sapp and S. D. Carlson, 1989, Photoreceptor maintenance and degeneration in the norpA (no receptor potential-A) mutant of Drosophila melanogaster, J. Neurogenetics. 5: 49–59.CrossRefGoogle Scholar
  28. 28.
    Colley, N. J., E. K. Baker, M. A. Stamnes and C. S. Zuker, 1991, The cyclophilin homolog ninoA is required in the secretory pathway, Cell. 67: 255–263.PubMedCrossRefGoogle Scholar
  29. 29.
    Stark, W. S., R. Sapp and D. Schilly, 1988, Rhabdomere turnover and rhodopsin cycle: maintenance of retinula cells in Drosophila melanogaster, J. Neurocyto. 17: 499–509.CrossRefGoogle Scholar
  30. 30.
    Ozaki, K., H. Nagatani, M. Ozaki and F. Tokunaga, 1993, Maturation of the major Drosophila rhodopsin, ninaE, requires chromophore 3-hydroxylretinal, Neuron. 10: 1113–1119.PubMedCrossRefGoogle Scholar
  31. 31.
    Huber, A., U. Wolfrum and R. Paulsen, 1994, Opsin maturation and targeting to rhabdomeral photoreceptor membranes requires the retinal chromophore, Eur. J. Cell Biol. 63: 219–229.PubMedGoogle Scholar
  32. 32.
    O’Tousa, J. E., 1991, Requirement of N-linked glycosylation site in Drosophila rhodopsin, Visual Neuroscience. 8: 385–390.CrossRefGoogle Scholar
  33. 33.
    Sung, C.-H., B. G. Schneider, N. Agarwal, D. S. Papermaster and J. Nathans, 1991, Functional heterogeneity of mutant rhodopsins responsible for automsomal retinitis pigmentosa, Proc. Natl. Acad. Sci. USA. 88: 8840–8844.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Phani Kurada
    • 1
  • Timothy D. Tonini
    • 1
  • Joseph E. O’Tousa
    • 1
  1. 1.Department of Biological SciencesUniversity of Notre DameNotre DameUSA

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