Hostname: page-component-586b7cd67f-2brh9 Total loading time: 0 Render date: 2024-11-24T04:03:26.679Z Has data issue: false hasContentIssue false
  • English
  • Français

Chemically induced retinal degeneration in the rdgB (retinal degeneration B) mutant of Drosophila

Published online by Cambridge University Press:  02 June 2009

Chaim T. Rubinstein ,
Shoshana Bar-Nachum ,
Zvi Selinger  and
Baruch Minke
Chaim T. Rubinstein
Affiliation:
Department of Physiology, The Hebrew University of Jerusalem, Israel
Shoshana Bar-Nachum
Affiliation:
Department of Physiology, The Hebrew University of Jerusalem, Israel
Zvi Selinger
Affiliation:
Department of Biological Chemistry, The Hebrew University of Jerusalem, Israel
Baruch Minke
Affiliation:
Department of Physiology, The Hebrew University of Jerusalem, Israel
Get access Rights & Permissions [Opens in a new window]

Abstract

Chemicals which affect different steps of the phototransduction cascade were used to identify the site of action of the rdgB gene product of Drosophila. In the rdgB mutant, the photoreceptor cells degenerate after several days of exposure to light, whereas raising the flies in the dark largely prevents the degeneration. In the rdgBKS222 mutant, which was used in the present studies, the light-induced degeneration is characterized by (1) selective degeneration of the peripheral but not the central photoreceptor cells; (2) random distribution of degenerated cells among ommatidia; and (3) the degeneration is specific to the rdgB but not the wild-type photoreceptor cells. In the present study, we show that application of specific chemical agents to the eyes of rdgBKS222 flies in the dark mimics the effects of light and causes retinal degeneration indistinguishable from light. The agents used in these studies are the metabolically stable GTP analogs GTPγS and Gpp(NH)p as well as fluoride ions, which are known to activate the transducing guanine nucleotide binding protein (G-protein of fly photoreceptors). It is unlikely that the chemically induced retinal degeneration is mediated by effects on energy metabolism, since application of the metabolic inhibitors CN-and 2-deoxy-D-glucose did not increase the extent of retinal degeneration over that observed in control flies treated with Ringer solution. The GDP analog GDPβS, which inhibits G-protein activity, greatly reduced the extent of retinal degeneration in the dark, over that observed in control flies treated with Ringer solution. These results suggest that activation of the G-protein precedes the step in the transduction cascade that leads to retinal degeneration and provides a powerful tool to investigate the molecular mechanism of light-induced degeneration in the rdgB mutant.

Keywords

Drosophilia mutantrdgBKS222PhototransductionGTPγSF−Retinal degeneration
Type
Research Article
Information
Visual Neuroscience , Volume 2 , Issue 6 , June 1989 , pp. 541 - 551
Copyright
Copyright © Cambridge University Press 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baer, K.M. & Saibil, H.R. (1988). Light and GTP-activated hydrolysis of phosphatidylinositol bisphosphate in squid photoreceptor membranes. Journal of Biological Chemistry 263, 17–20.CrossRefGoogle ScholarPubMed
Bentrop, J. & Paulsen, R. (1988). Light-modulated ADP ribosilation: protein phosphorylation and protein binding in isolated fly photo-receptor membranes. European Journal of Biochemistry 161, 61–67.CrossRefGoogle Scholar
Bigay, J., Deterre, P., Pfister, C. & Chabre, M. (1985). Fluoro-aluminates activate transducin-GDP by mimicking the γ-phosphate of GTP in its binding site. FEBS Letters 191, 181–185.CrossRefGoogle ScholarPubMed
Blest, A.D. & Eddey, W. (1984). The extrarhabdomeral cytoskeleton in photoreceptors of Diptera. II. Plasmalemmal undercoats. Proceedings of the Royal Society B London 220, 353–359.Google Scholar
Bloomquist, B.T., Shortridge, S.O., Sehneuwly, S., Pedrew, M., Montell, C., Steller, H., Rubin, G. & Pak, W.L. (1988). Isolation of a putative phospholipase C gene of Drosophila, norpA and its role in phototransduction. Cell 54, 723–733.CrossRefGoogle ScholarPubMed
Blumenfeld, A., Erusalimsky, J., Heichal, O., Selinger, Z. & Minke, B. (1985). Light-activated guanosine triphosphatase in Musca eye membranes resembles the prolonged depolarizing after-potential in photoreceptor cells. Proceedings of The National Academy of Sciences of the U.S.A. 82, 7116–7120.CrossRefGoogle Scholar
Bolsover, S.R. & Brown, J.E. (1982). Injection of guanosine and adenosine nucleotide into Limulus ventral photoreceptor cells. Journal of Physiology 332, 325–342.CrossRefGoogle ScholarPubMed
Brown, J.E., Rubin, L.J., Ghalayini, A.J., Traver, A.L., Irvine, R.F., Berridge, M.J. & Anderson, R.E. (1984). Myo-inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors. Nature 311, 160–163.CrossRefGoogle ScholarPubMed
Calhoon, T., Tsuda, M. & Ebrey, T.G. (1980). A light-activated GTPase from octopus photoreceptors. Biochemical and Biophysical Research Communications 94, 1452–1457.CrossRefGoogle ScholarPubMed
Devary, O., Heichal, O., Blumenfeld, A., Cassel, D., Suss, E., Barash, S., Rubinstein, C.T., Minke, B. & Selinger, Z. (1987). Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors. Proceedings of the National Academy of Sciences of the U.S.A. 84, 6939–6943.CrossRefGoogle ScholarPubMed
Eckstein, F., Cassel, D., Levkovitz, H., Lowe, M. & Selinger, Z. (1979). Guanosine 5'-0-(2-thiodiphosphate), an inhibitor of adenyl-ate cyclase stimulation by guanine nucleotides and fluoride ions. Journal of Biological Chemistry 254, 9829–9834.CrossRefGoogle Scholar
Fein, A. & Corson, D.W. (1981). Excitation of Limulus photoreceptors by vanadate and by a hydrolysis resistant analog of guanosine triphosphate. Science 212, 555–557.CrossRefGoogle ScholarPubMed
Fein, A., Payne, R., Corson, D.W., Berridge, M.J. & Irvine, R.F. (1984). Photoreceptor excitation and adaptation by inositol 1, 4, 5-trisphosphate. Nature 311, 157–160.CrossRefGoogle ScholarPubMed
Fein, A. (1986). Blockade of visual excitation and adaptation in Limulus photoreceptors by GDPβS. Science 232, 1543–1545.CrossRefGoogle ScholarPubMed
Feller, W. (1957). An Introduction to Probability Theory and Its Application Vol. I New York & London: John Wiley & Sons, Inc.Google Scholar
Harris, W.A. & Stark, W.S. (1977). Hereditary retinal degeneration in Drosophila melanogaster. A mutant defect associated with the phototransduction process. Journal of General Physiology 69, 261–291.CrossRefGoogle ScholarPubMed
Hotta, Y. & Benzer, S. (1970). Genetic dissection of the Drosophila nervous system by means of mosaics. Proceedings of the National Academy of Sciences of the U.S.A. 67, 1156–1163.CrossRefGoogle ScholarPubMed
Lisman, J. (1985). The role of metarhodopsin in the generation of spontaneous quantum bumps in ultraviolet receptors of Limulus median eye. Evidence for reverse reactions into an active state. Journal of General Physiology 85, 171–187.CrossRefGoogle ScholarPubMed
Minke, B. & Stephenson, R.S. (1985). The characteristics of chemically induced noise in Musca photoreceptors. Journal of Comparative Physiology 156, 339–356.CrossRefGoogle Scholar
Payne, R. (1981). Suppression of noise in photoreceptors by oxidative metabolism. Journal of Comparative Physiology 142, 181–188.CrossRefGoogle Scholar
Payne, R. (1982). Fluoride blocks an inactivation step of transduction in a locust photoreceptor. Journal of Physiology 325, 261–279.CrossRefGoogle Scholar
Payne, R. (1986). Phototransduction by microvillar photoreceptors of invertebrates: mediation of a visual cascade by inositol trisphosphate. Photobiochemistry and Photobiophysics 13, 373–397.Google Scholar
Rubinstein, C.T., Bar-Nachum, S., Selinger, Z. & Minke, B. (1989). Light-induced retinal degeneration in rdgB (retinal degeneration B) mutant of Drosophila: electrophysiological and morphological manifestations of degeneration. Visual Neuroscience 2, 529–539.CrossRefGoogle ScholarPubMed
Saibil, H.R. & Michel-Villaz, M. (1984). Squid rhodopsin and GTP-binding protein crossreact with vertebrate photoreceptors enzymes. Proceedings of the National Academy of Sciences of the U.S.A. 81, 5111–5115.CrossRefGoogle ScholarPubMed
Selinger, Z. & Minke, B. (1989). Inositol lipid cascade of vision studied in mutant flies. Cold Spring Harbor Symposia on Quantitative Biology Vol. LIII (in press).Google Scholar
Stark, W.S. & Carlson, S.D. (1982). Ultrastructural pathology of the compound eye and optic neuropile of the retinal degenerative mutant (rdgBKS222) Drosophila melanogaster. Cell and Tissue Research 225, 11–22.CrossRefGoogle Scholar
Stern, J., Chinn, K., Robinson, P. & Lisman, J. (1975). The effect of nucleotides on the rate of spontaneous quantum bumps in Limulus ventral photoreceptors. Journal of General Physiology 85, 157–169.CrossRefGoogle Scholar
Vandenberg, C.A. & Montal, M. (1984). Light-regulated biochemical events in invertebrate photoreceptors. I. Light-activated guanosinetri-phosphatase, guanine nucleotide binding, and cholera toxin catalyzed labeling of squid photoreceptor membranes. Biochemistry 23, 2339–2347.CrossRefGoogle ScholarPubMed
Weyrauther, E., Roebroek, J.G.H. & Stavenga, D.G. (1989). Dye transport across the retinal basement membrane of the blowfly Calliphora erythrocephala. Journal of Experimental Biology (in press).CrossRefGoogle Scholar
Wilcox, M. & Franceschini, N. (1984 a). Stimulated drug uptake in a photoreceptor cell. Neuroscience Letters 50, 187–192.CrossRefGoogle Scholar
Wilcox, M. & Franceschini, N. (1984 b). Illumination induces dye incorporation in photoreceptor cells. Science 255, 851–854.CrossRefGoogle Scholar