1. G. Haider, P. Callaerts, W.J. Gehring (1995). Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science, 267, 1788-1792.

2. P. Callaerts, G. Haider, W.J. Gehring (1997). PAX-6 in development and evolution. Annu. Rev. Neurosci., 20, 483-532.

3. W.J. Gehring, K. Ikeo (1997). Pax 6: mastering eye morphogenesis and eye evolution. Trends. Genet., 15, 371-377.

4. W.J. Gehring (2002). The genetic control of eye development and its implications for the evolution of the various eye-types. Int. J. Dev. Biol., 46, 65-73.

5. T.W. Cronin, M. Jarvilehto, M. Weckstrom, A.B. Lall (2000). Tuning of photoreceptor spectral sensitivity in fireflies (Coleóptera: Lampyridae). J. Comp. Physiol. [A], 186, 1-12.

6. W.L. Pak (1995). Drosophila in vision research. The Friedenwald Lecture. Invest. Ophthalmol. Vis. Set, 36, 2340-2357.

7. R. Ranganathan, D.M. Malicki, C.S. Zuker (1995). Signal transduction in Drosophila photoreceptors. Annu. Rev. Neurosci., 18, 283 317.

8. K. Scott, C. Zuker (1997). Lights out: deactivation of the phototransduction cascade. Trends Biochem. Sci., 22, 350-354.

9. S. Tsunoda, C.S. Zuker (1999). The organization of INAD-signaling complexes by a multivalent PDZ domain protein in Drosophila photoreceptor cells ensures sensitivity and speed of signaling. Cell Calcium, 26, 165-171.

10. C. Montell (2000). Regulation of Drosophila visual transduction through a supramolecular signaling complex. In: P.M. Conn, A.R. Means (Eds), Principles of Molecular Regulation (pp. 85-97). Humana Press, Totowa, N.J.

11. R. Paulsen, M. Bähner, A. Huber, M. Schillo, S. Schulz, R. Wottrich, J. Bentrop (2001). The molecular design of a visual cascade: Molecular stages of phototrans-duction in Drosophila. In: C. Musio (Ed.), Vision: The Approach of Biophysics and Neurosciences (pp. 41-59). World Scientific, Singapore.

12. R. Paulsen, M. Bähner, J. Bentrop, M. Schillo, S. Schulz, A. Huber (2001). The molecular design of a visual cascade: Assembly of the Drosophila phototrans-duction pathway into a supramolecular signaling complex. In: C. Musio (Ed.), Vision: The Approach of Biophysics and Neurosciences (pp. 60-73). World Scientific, Singapore.

13. R.C. Hardie, P. Raghu (2001).Visual transduction in Drosophila. Nature, 186-193.

14. W. Gärtner (2000). Invertebrate visual pigments. In: D.G. Stavenga, W.J. de Grip, E.N.J. Pugh (Eds), Handbook of Biological Physics (pp. 297-388). Elsevier Science B.V., Amsterdam.

15. I.M. Pepe (2001). Recent advances in our understanding of rhodopsin and phototransduction. Prog. Retin. Eye Res., 20, 733-759.

16. B. Minke, R.C. Hardie (2000). Genetic Dissection of Drosophila Phototransduction. In: D.G. Stavenga, W.J. DeGrip, E.N.J. Pugh (Eds), Handbook of Biological Physics (pp. 449-525). Elsevier Science B.V., Amsterdam.

17. D.G. Stavenga, J. Oberwinkler, M. Postma (2000). Modeling Primary Visual Processes in Insect Photoreceptors. In: D.G. Stavenga, W.J. DeGrip, E.N.J. Pugh (Eds), Handbook of Biological Physics (pp. 527-574). Elsevier Science B.V., Amsterdam, London, New York, Oxford, Paris, Shannon, Tokyo.

18. R.C. Hardie (2001). Phototransduction in Drosophila melanogaster. J. Exp. Biol., 204, 3403-3409.

19. T.P. Sakmar (1998). Rhodopsin: a prototypical G protein-coupled receptor. Prog. Nucleic. Acid. Res. Mol. Biol, 59, 1-34.

20. J.S. Ascher, B.N. Danforth, S. Ji (2001). Phylogenese utility of the major opsin in bees (Hymenoptera: Apoidea): a reassessment. Mol. Phylogenet. Evol., 19, 76-93.

21. T. Kusakabe, R. Kusakabe, I. Kawakami, Y. Satou, N. Satoh, M. Tsuda (2001). Ci-opsinl, a vertebrate-type opsin gene, expressed in the larval ocellus of the ascidian Ciona intestinalis. FEBS Lett., 506, 69-72.

22. T. Kusakabe, R. Yoshida, I. Kawakami, R. Kusakabe, Y. Mochizuki, L. Yamada, Shin, Y. Kohara, N. Satoh, et al., (2002). Gene expression profiles in tadpole larvae of Ciona intestinalis. Dev. Biol., 242, 188-203.

23. W.H. Chou, A. Huber, J. Bentrop, S. Schulz, K. Schwab, L.V. Chadwell, R. Paulsen, S.G. Britt (1999). Patterning of the R7 and R8 photoreceptor cells of Drosophila: evidence for induced and default cell-fate specification. Development, 126, 607-616.

24. E. Salcedo, A. Huber, S. Henrich, L.V. Chadwell, W.H. Chou, R. Paulsen, S.G. Britt (1999). Blue-and green-absorbing visual pigments of Drosophila: ectopic expression and physiological characterization of the R8 photoreceptor cell-specific Rh5 and Rh6 rhodopsins. J. Neurosci, 19, 10716-10726.

25. M.R. Chase, R.R. Bennett, R.H. White (1997). Three opsin-encoding cDNAS from the compound eye of Manduca sexta. J. Exp. Biol., 200, 2469-2478.

26. A.D. Briscoe, L. Chittka (2001). The evolution of color vision in insects. Annu. Rev. Entomol., 46, 471-510.

27. F. Pichaud, A. Briscoe, C. Desplan (1999). Evolution of color vision. Curr. Opin. Neurobiol., 9, 622-627.

28. S. Yokoyama, Y. Shi (2000). Genetics and evolution of ultraviolet vision in vertebrates. FEBS Lett., 486, 167-172.

29. S. Yokoyama (2000). Molecular evolution of vertebrate visual pigments. Prog. Retin. Eye Res., 19, 385^119.

30. Y. Shi, F.B. Radlwimmer, S. Yokoyama (2001). Molecular genetics and the evolution of ultraviolet vision in vertebrates. Proc. Natl. Acad .Sci. U.S.A., 98, 11731-11736.

31. D. Kojima, A. Terakita, T. Ishikawa, Y. Tsukahara, A. Maeda, Y. Shichida (1997). A novel Go-mediated phototransduction cascade in scallop visual cells. J. Biol. Chem., 272, 22979-22982.

32. M.D. Adams, S.E. Celniker, R.A. Holt, C.A. Evans, J.D. Gocayne, P.G. Amanatides, S.E. Scherer, P.W. Li, R.A. Hoskins, et al., (2000). The genome sequence of Drosophila melanogaster. Science, 287, 2185-2195.

33. J.P. Carulli, D.M. Chen, W.S. Stark, D.L. Hartl (1994). Phylogeny and physiology of Drosophila opsins. J. Mol. Evol., 38, 250-262.

34. D. Kojima, A. Terakita, T. Ishikawa, Y. Tsukahara, A. Maeda, Y. Shichida

(1997). A novel Go-mediated phototransduction cascade in scallop visual cells. J. Biol. Chem., 272, 22979-22982.

35. J.E. O'Tousa, W. Baehr, R.L. Martin, J. Hirsh, W.L. Pak, M.L. Applebury (1985). The Drosophila ninaE gene encodes an opsin. Cell, 40, 839-850.

36. C.S. Zuker, A.F. Cowman, G.M. Rubin (1985). Isolation and structure of a rhodopsin gene from D. melanogaster. Cell, 40, 851-858.

37. C.S. Zuker, C. Montell, K. Jones, T. Laverty, G.M. Rubin (1987). A rhodopsin gene expressed in photoreceptor cell R7 of the Drosophila eye: homologies with other signal-transducing molecules. J. Neurosci, 7, 1550-1557.

38. C. Montell, K. Jones, C. Zuker, G. Rubin (1987). A second opsin gene expressed in the ultraviolet-sensitive R7 photoreceptor cells of Drosophila melanogaster. J. Neurosci, 7, 1558-1566.

39. W.H. Chou, K.J. Hall, D.B. Wilson, C.L. Wideman, S.M. Townson, L.V. Chadwell, S.G. Britt (1996). Identification of a novel Drosophila opsin reveals specific patterning of the R7 and R8 photoreceptor cells. Neuron, 17, 1101-1115.

40. D. Papatsenko, G. Sheng, C. Desplan (1997). A new rhodopsin in R8 photoreceptors of Drosophila: evidence for coordinate expression with Rh3 in R7 cells. Development, 124, 1665-1673.

41. A. Huber, S. Schulz, J. Bentrop, C. Groell, U. Wolfrum, R. Paulsen (1997). Molecular cloning of Drosophila Rh6 rhodopsin: the visual pigment of a subset of R8 photoreceptor cells. FEBS Lett., 406, 6-10.

42. J.A. Pollock, S. Benzer (1988). Transcript localization of four opsin genes in the three visual organs of Drosophila; RH2 is ocellus specific. Nature, 333, 779-782.

43. E. Salcedo, A. Huber, S. Henrich, L.V. Chadwell, W.H. Chou, R. Paulsen, S.G. Britt (1999). Ectopic expression and physiological characterization of the R8 photoreceptor cell-specific Rh5 and Rh6 rhodopsins of Drosophila. J. Neurosci., 24, 10716-10726.

44. A. Engels, H. Reichert, W.J. Gehring, W. Gartner (2000). Functional expression of a locust visual pigment in transgenic Drosophila melanogaster. Eur. J. Biochem., 267, 1917-1922.

45. S.M. Townson, B.S. Chang, E. Salcedo, L.V. Chadwell, N.E. Pierce, S.G. Britt

(1998). Honeybee blue- and ultraviolet-sensitive opsins: cloning, heterologous expression in Drosophila, and physiological characterization. J. Neurosci., 18, 2412-2422.

46. H.Y. Chang, D.F. Ready (2000). Rescue of photoreceptor degeneration in rhodopsin-null Drosophila mutants by activated racl. Science, 290, 1978-1980.

47. J. Bentrop, K. Schwab, W.L. Pak, R. Paulsen (1997). Site-directed mutagenesis of highly conserved amino acids in the first cytoplasmic loop of Drosophila Rhl opsin blocks rhodopsin synthesis in the nascent state. EM BO J., 16, 1600-1609.

48. T. Washburn, J.E. O'Tousa (1989). Molecular defects in Drosophila rhodopsin mutants. J. Biol. Chem., 264, 15464-15466.

49. J. Bentrop (1998). Rhodopsin mutations as the cause of retinal degeneration. Classification of degeneration phenotypes in the model system Drosophila melanogaster. Acta Anat., 162, 85-94.

50. R. Hubbard, R.C.C. StGeorge (1958). The rhodopsin system of the squid. J. Gen. Physiol., 41, 501-528.

51. R. Paulsen, J. Schwemer (1983). Biogenesis of blowfly photoreceptor membranes is regulated by 11-cis-retinal. Eur. J. Biochem., 137, 609-614.

52. K. Vogt (1983). Is the fly visual pigment a rhodopsin? Z. Naturforsch. [C], 38, 329-333.

53. S. Matsui, M. Seidou, I. Uchiyama, N. Sekiya, K. Hiraki, K. Yoshihara, Y. Kito (1988). 4-Hydroxyretinal, a new visual pigment chromophore found in the bioluminescent squid, Watasenia scintillans. Biochim. Biophys. Acta, 966, 370-374.

54. T. Kitagawa, M. Tsuda (1980). Resonance Raman spectra of octopus acid and alkaline metarhodopsins. Biochim. Biophys. Acta, 624, 211 217.

55. C. Pande, A. Pande, K.T. Yue, R. Callender, T.G. Ebrey, M. Tsuda (1987). Resonance Raman spectroscopy of octopus rhodopsin and its photoproducts. Biochemistry, 26, 4941-4947.

56. C. Pande, H. Deng, P. Rath, R.H. Callender, J. Schwemer (1987). Resonance raman spectroscopy of an ultraviolet-sensitive insect rhodopsin. Biochemistry, 26, 7426-7430.

57. S. Nishimura, H. Kandori, M. Nakagawa, M. Tsuda, A. Maeda (1997). Structural dynamics of water and the peptide backbone around the Schiff base associated with the light-activated process of octopus rhodopsin. Biochemistry, 36, 864-870.

58. B.W. Vought, E. Salcedo, L.V. Chadwell, S.G. Britt, R.R. Birge, B.E. Knox (2000). Characterization of the primary photointermediates of Drosophila rhodopsin. Biochemistry, 39, 14128-14137.

59. E.A. Zhukovsky, D.D. Oprian (1989). Effect of carboxylic acid side chains on the absorption maximum of visual pigments. Science, 246, 928-930.

60. T.P. Sakmar, R.R. Franke, H.G. Khorana (1989). Glutamic acid-113 serves as the retinylidene Schiff base counterion in bovine rhodopsin. Proc. Natl. Acad. Sci. U.S.A., 86, 8309-8313.

61. J. Nathans (1990). Determinants of visual pigment absorbance: identification of the retinylidene Schiff s base counterion in bovine rhodopsin. Biochemistry, 29, 9746-9752.

62. M. Nakagawa, T. Iwasa, S. Kikkawa, M. Tsuda, T.G. Ebrey (1999). How vertebrate and invertebrate visual pigments differ in their mechanism of photoactivation. Proc. Natl. Acad. Sci. U.S.A., 96, 6189-6192.

63. K. Hamdorf, R. Paulsen, J. Schwemer (1973). Photoregeneration and sensitivity control of photoreceptors in invertebrates. In: H. Langer (Ed.), Biochemistry and Physiology of Visual Pigments (pp. 155-166). Springer Verlag, Berlin.

64. K. Hamdorf (1979). The Physiology of Invertebrate Visual Pigments. In: H. Autrum (Ed.), Handbook of Sensory Physiology, (pp. 145-224). Springer-Verlag, Berlin.

65. P. Hillman, S. Hochstein, B. Minke (1983). Transduction in invertebrate photoreceptors: role of pigment bistability. Physiol. Rev., 63, 668-772.

66. D.G. Stavenga, J. Schwemer (1984). Visual Pigments of Invertebrates. In: M.A. Ali (Ed.), Photoreception and Vision in Invertebrates (pp. 11-61). Plenum Publishing, New York.

67. K. Ozaki, H. Nagatani, M. Ozaki, F. Tokunaga (1993). Maturation of major Drosophila rhodopsin, ninaE, requires chromophore 3-hydroxyretinal. Neuron, 10, 1113 1119.

68. A. Huber, U. Wolfrum, R. Paulsen (1994). Opsin maturation and targeting to rhabdomeral photoreceptor membranes requires the retinal chromophore. Eur. J. Cell Biol., 63, 219-229.

69. J. Schwemer (1984). Renewal of visual pigment in photoreceptors of blowfly. J. Comp. Physiol. [A], 154, 535-547.

70. P.G. Alloway, L. Howard, P.J. Dolph (2000). The formation of stable rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell degeneration. Neuron, 28, 129-138.

71. T.G. Ebrey (2000). pKa of the protonated Schiff base of visual pigments. Methods Enzymol., 315, 196-207.

72. T. Okada, O.P. Ernst, K. Palczewski, K.P. Hofmann (2001). Activation of rhodopsin: new insights from structural and biochemical studies. Trends. Biochem. Set, 26, 318-324.

73. A. Kiselev, S. Subramaniam (1994). Activation and regeneration of rhodopsin in the insect visual cycle. Science, 266, 1369-1373.

74. A. Davies, B.E. Gowen, A.M. Krebs, G.F. Schertler, H.R. Saibil (2001). Three-dimensional structure of an invertebrate rhodopsin and basis for ordered alignment in the photoreceptor membrane. J. Mol. Biol., 314, 455^163.

75. C. Venien-Bryan, A. Davies, K. Langmack, J. Baverstock, A. Watts, D. Marsh, H. Saibil (1995). Effect of the C-terminal proline repeats on ordered packing of squid rhodopsin and its mobility in membranes. FEBS Lett., 359, 45^49.

76. J.M. Baldwin, G.F. Schertler, V.M. Unger (1997). An alpha-carbon template for the transmembrane helices in the rhodopsin family of G-protein-coupled receptors. ./. Mol. Biol., 272, 144-164.

77. K. Palczewski, T. Kumasaka, T. Hori, C.A. Behnke, H. Motoshima, B.A. Fox, T. Le, I, D.C. Teller, T. Okada, et al. (2000). Crystal structure of rhodopsin: A G protein-coupled receptor. Science, 289, 739-745.

78. J.S. Lott, J.I. Wilde, A. Carne, N. Evans, J.B. Findlay (1999). The ordered visual transduction complex of the squid photoreceptor membrane. Mol. Neurobiol., 20 61-80.

79. Y. Ovchinnikov, N.G. Abdulaev, A.S. Zolotarev, I.D. Artamonov, I.A. Bespalov, A.E. Dergachev, M. Tsuda (1988). Octopus rhodopsin. Amino acid sequence deduced from cDNA. FEBS Lett., 232, 69-72.

80. M. Nakagawa, T. Iwasa, S. Kikkawa, T. Takao, Y. Shimonishi, M. Tsuda (1997). Identification of two palmitoyl groups in octopus rhodopsin. Photochem. Photobiol., 65, 187-191.

81. Y. Zhang, T. Iwasa, M. Tsuda, A. Kobata, S. Takasaki (1997). A novel mono-antennary complex-type sugar chain found in octopus rhodopsin: occurrence of the Gaipi^Fuc group linked to the proximal N-acetylamine residue of the trimannosyl core. Glycobiology, 7, 1153-1158.

82. A. Huber, D.P. Smith, C.S. Zuker, R. Paulsen (1990). Opsin of Calliphora peripheral photoreceptors Rl-6. Homology with Drosophila Rhl and posttranslational processing. J. Biol. Chem., 265, 17906-17910.

K. Katanosaka, F. Tokunaga, S. Kawamura, K. Ozaki (1998). N-linked glycosylation of Drosophila rhodopsin occurs exclusively in the amino-terminal domain and functions in rhodopsin maturation. FEBS Lett., 424, 149 154. J.E. O'Tousa (1992). Requirement of N-linked glycosylation site in Drosophila rhodopsin. Vis. Neurosci, 8, 385-390.

E.K. Baker, N.J. Colley, C.S. Zuker (1994). The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J., 13, 4886^4895.

S. Schneuwly, R.D. Shortridge, D.C. Larrivee, T. Ono, M. Ozaki, W.L. Pak (1989). Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein). Proc. Natl. Acad. Sei. U.S.A., 86, 5390-5394. M. Nakagawa, T. Miyamoto, R. Kusakabe, S. Takasaki, T. Takao, Y. Shichida, M. Tsuda (2001). O-Glycosylation of G-protein-coupled receptor, octopus rhodopsin. Direct analysis by FAB mass spectrometry. FEBS Lett., 496, 19-24. H. Kühn, W.J. Dreyer (1972). Light dependent phosphorylation of rhodopsin by ATP. FEBS Lett., 20, 1-6.

D. Bownds, J. Dawes, J. Miller, M. Stahlman (1972). Phosphorylation of frog photoreceptor membranes induced by light. Nat. New Biol., 237, 125-127. R.N. Frank, H.D. Cavanagh, K.R. Kenyon (1973). Light-stimulated phosphorylation of bovine visual pigments by adenosine triphosphate. J. Biol. Chem., 248, 596-609.

R. Paulsen, I. Hoppe (1978). Light-activated phosphorylation of cephalopod rhodopsin. FEBS Lett., 96, 55-58.

M. Tsuda, T. Tsuda, H. Hirata (1989). Cyclic nucleotides and GTP analogues stimulate light-induced phosphorylation of octopus rhodopsin. FEBS Lett., 257, 38^0.

R. Paulsen, J. Bentrop (1984). Reversible phosphorylation of opsin induced by irradiation of blowfly retinae. J. Comp. Physiol. [A J, 155, 39-45. J. Bentrop, R. Paulsen (1986). Light-modulated ADP-ribosylation, protein phosphorylation and protein binding in isolated fly photoreceptor membranes. Eur. J. Biochem., 161, 61-67.

J. Bentrop, A. Plangger, R. Paulsen (1993). An arrestin homolog of blowfly photoreceptors stimulates visual-pigment phosphorylation by activating a membrane-associated protein kinase. Eur. J. Biochem., 216, 67-73. A. Plangger, D. Malicki, M. Whitney, R. Paulsen (1994). Mechanism of arrestin 2 function in rhabdomeric photoreceptors. J. Biol. Chem., 269, 26969-26975. H. Ohguro, N. Yoshida, H. Shindou, J.W. Crabb, K. Palczewski, M. Tsuda (1998). Identification of a single phosphorylation site within octopus rhodopsin. Photochem. Photobiol, 68, 824-828.

A. Kiselev, M. Socolich, J. Vinos, R.W. Hardy, C.S. Zuker, R. Ranganathan (2000). A molecular pathway for light-dependent photoreceptor apoptosis in Drosophila. Neuron, 28, 139-152.

J. Nguyen-Legros, D. Hicks (2000). Renewal of photoreceptor outer segments and their phagocytosis by the retinal pigment epithelium. Int. Rev. Cytol., 196, 245-313.

F. Pichaud, C. Desplan (2001). A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia. Development, 128, 815-826.

F. Pichaud, J. Treisman, C. Desplan (2001). Reinventing a common strategy for patterning the eye. Cell, 105, 9 12.

102. R. Paulsen (1984). Spectral characteristics of isolated blowfly rhabdoms. J. Comp. Physiol [A], 155, 47-55.

103. L. Huang, H. Deng, Y. Koutalos, T. Ebrey, M. Groesbeek, J. Lugtenburg, M. Tsuda, R.H. Callender (1997). A resonance Raman study of the C=C stretch modes in bovine and octopus visual pigments with isotopically labeled retinal chromophores. Photochem. Photobiol., 66, 747-754.

104. Y. Nishioku, M. Nakagawa, M. Tsuda, M. Terazima (2001). A spectrally silent transformation in the photolysis of octopus rhodopsin: a protein conformational change without any accompanying change of the chromophore's absorption. Biophys J., 80, 2922-2927.

105. G.G. Kochendoerfer, S.W. Lin, T.P. Sakmar, R.A. Mathies (1999). How color visual pigments are tuned. Trends. Biochem. Sei., 24, 300-305.

106. R. Feiler, W.A. Harris, K. Kirschfeld, C. Wehrhahn, C.S. Zuker (1988). Targeted misexpression of a Drosophila opsin gene leads to altered visual function. Nature, 333, 737-741.

107. R. Feiler, R. Bjornson, K. Kirschfeld, D. Mismer, G.M. Rubin, D.P. Smith, M. Socolich, C.S. Zuker (1992). Ectopic expression of ultraviolet-rhodopsins in the blue photoreceptor cells of Drosophila'. visual physiology and photochemistry of transgenic animals. J. Neuroscl, 12, 3862-3868.

108. S.G. Britt, R. Feiler, K. Kirschfeld, C.S. Zuker (1993). Spectral tuning of rhodopsin and metarhodopsin in vivo. Neuron, 11, 29-39.

109. W. Gärtner, D. Ullrich, K. Vogt (1991). Quantum yield of CHAPSO-solubilized rhodopsin and 3-hydroxy retinal containing bovine opsin. Photochem. Photobiol., 54, 1047-1055.

110. K. Kirschfeld, N. Franceschini (1977). Evidence for a sensitising pigment in fly photoreceptors. Nature, 269, 386-390.

111. B. Minke, K. Kirschfeld (1979). The contribution of a sensitizing pigment to the photosensitivity spectra of fly rhodopsin and metarhodopsin. J. Gen. Physiol., 73, 517-540.

112. K. Vogt, K. Kirschfeld (1983). Sensitizing pigment in the fly. Biophys. Struct. Meek, 9, 319-328.

113. K. Kirschfeld (1986). Activation of Visual Pigment: Chromophore Structure and Function, In: H. Stieve (Ed), The Molecular Mechanism of Photoreception (pp. 31-49). Springer-Verlag, Berlin.

114. K. Hamdorf, P. Hochstrate, G. Höglund, M. Moser, S. Sperber, P. Schlecht (1992). Ultra-violet sensitizing pigment in blowfly photoreceptors Rl-6: probable nature and binding sites. J. Comp. Physiol. [A], 171, 601-615.

115. J. Kitamoto, K. Sakamoto, K. Ozaki, Y. Mishina, K. Arikawa (1998). Two visual pigments in a single photoreceptor cell: identification and histological localization of three mRNAs encoding visual pigment opsins in the retina of the butterfly Papilio xuthus. J. Exp. Biol., 201, 1255-1261.

116. S.L. Fong, P.G. Lee, K. Ozaki, R. Hara, T. Hara, C.D. Bridges (1988). IRBP-like proteins in the eyes of six cephalopod species-immunochemical relationship to vertebrate interstitial retinol-binding protein (IRBP) and cephalopod retinal-binding protein. Vision Res., 28, 563-573.

117. A. Terakita, R. Hara, T. Hara (1989). Retinal-binding protein as a shuttle for retinal in the rhodopsin-retinochrome system of the squid visual cells. Vision Res., 29, 639-652.

118. M. Tsuda, T. Tsuda (1990). Two distinct light regulated G-proteins in octopus photoreceptors. Biochim. Biophys. Acta, 1052, 204-210.

119. J.D. Pottinger, N.J. Ryba, J.N. Keen, J.B. Findlay (1991). The identification and purification of the heterotrimeric GTP-binding protein from squid (Loligo forbesi) photoreceptors. Biochem. J., 279, 323-326.

120. T. Suzuki, A. Terakita, K. Narita, K. Nagai, Y. Tsukahara, Y. Kito (1995). Squid photoreceptor phospholipase C is stimulated by membrane Gq alpha but not by soluble Gq alpha. FEBS Lett., 377, 333-337.

121. T. Suzuki, K. Narita, A. Terakita, E. Takai, K. Nagai, Y. Kito, Y. Tsukahara (1999). Regulation of squid visual phospholipase C by activated G-protein alpha. Comp. Biochem. Physiol. A. Mol. Integr. Physiol., 122, 369-374.

122. S. Kikkawa, K. Tominaga, M. Nakagawa, T. Iwasa, M. Tsuda (1996). Simple purification and functional reconstitution of octopus photoreceptor Gq, which couples rhodopsin to phospholipase C. Biochemistry, 35, 15857 15864.

123. L.H. Mayeenuddin, C. Bamsey, J. Mitchell (2001). Retinal phospholipase C from squid is a regulator of Gq alpha GTPase activity. Neurochem. 78, 1350-1358.

124. A. Terakita, T. Hariyama, Y. Tsukahara, Y. Katsukura, H. Tashiro (1993). Interaction of GTP-binding protein Gq with photoactivated rhodopsin in the photoreceptor membranes of crayfish. FEBS Lett., 330, 197-200.

125. A. Terakita, H. Takahama, T. Hariyama, T. Suzuki, Y. Tsukahara (1998). Lightregulated localization of the beta-subunit of Gq-type G-protein in the crayfish photoreceptors. J. Comp. Physiol. [A], 183, 411 417.

126. O. Devary, O. Heichal, A. Blumenfeld, D. Cassel, E. Suss, S. Barash, C.T. Rubinstein, B. Minke, Z. Selinger (1987). Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors. Proc. Natl. Acad. Sci. U.S.A., 84, 6939-6943.

127. Y.J. Lee, M.B. Dobbs, M.L. Verardi, D R. Hyde (1990). dgq: a Drosophila gene encoding a visual system-specific G alpha molecule. Neuron, 5, 889-898.

128. K. Scott, A. Becker, Y. Sun, R. Hardy, C. Zuker (1995). Gq alpha protein function in vivo: genetic dissection of its role in photoreceptor cell physiology. Neuron, 15, 919-927.

129. B.T. Bloomquist, R.D. Shortridge, S. Schneuwly, M. Perdew, C. Montell, H. Steller, G. Rubin, W.L. Pak (1988). Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Cell, 54, 723-733.

130. R.D. Shortridge, J. Yoon, C.R. Lending, B.T. Bloomquist, M.H. Perdew, W.L. Pak (1991). A Drosophila phospholipase C gene that is expressed in the central nervous system. J. Biol Chem., 266, 12474-12480.

131. S. Schneuwly, M.G. Burg, C. Lending, M.H. Perdew, W.L. Pak (1991). Properties of photoreceptor-specific phospholipase C encoded by the norpA gene of Drosophila melanogaster. J. Biol. Chem., 266, 24314—24319.

132. R.R. McKay, D.M. Chen, K. Miller, S. Kim, W.S. Stark, R.D. Shortridge (1995). Phospholipase C rescues visual defect in norpA mutant of Drosophila melanogaster. J. Biol. Chem., 270, 13271-13276.

133. M.T. Pearn, L.L. Randall, R.D. Shortridge, M.G. Burg, W.L. Pak (1996). Molecular, biochemical, and electrophysiological characterization of Drosophila norpA mutants. J. Biol Chem., 271, 4937-4945.

134. Z. Selinger, B. Minke (1988). Inositol lipid cascade of vision studied in mutant flies. Cold Spring Harb. Symp. Quant. Biol, 53 (Pt 1), 333-341.

135. Y.J. Lee, S. Shah, E. Suzuki, T. Zars, P.M. O'Day, D.R. Hyde (1994). The Drosophila dgq gene encodes a G alpha protein that mediates phototransduction. Neuron, 13, 1143-1157.

136. S. Yarfitz, G.A. Niemi, J.L. McConnell, C.L. Fitch, J.B. Hurley (1991). A G beta protein in the Drosophila compound eye is different from that in the brain.

137. S. Schulz, A. Huber, K. Schwab, R. Paulsen (1999). A novel Ggamma isolated from Drosophila constitutes a visual G protein gamma subunit of the fly compound eye. J. Biol. Chem., 274, 37605-37610.

138. N.J. Ryba, J.B. Findlay, J.D. Reid (1993). The molecular cloning of the squid (Loligo forbesi) visual Gq-alpha subunit and its expression in Saccharomyces cerevisiae. Biochem. J., 292, 333-341.

139. T. Iwasa, T. Yanai, M. Nakagawa, S. Kikkawa, S. Obata, J. Usukura, M. Tsuda (2000). G protein a subunit genes in Octopus photoreceptor cells. Zool. Sci, 17, 711-716.

140. N.J. Ryba, J.D. Pottinger, J.N. Keen, J.B. Findlay (1991). Sequence of the beta-subunit of the phosphatidylinositol-specific phospholipase C-directed GTP-binding protein from squid (Loligo forbesi) photoreceptors. Biochem. J., 273, 225-228.

141. J.S. Lott, N.J. Ryba, J.D. Pottinger, J.N. Keen, A. Carne, J.B. Findlay (1992). The gamma-subunit of the principal G-protein from squid (Loligo forbesi) photoreceptors contains a novel N-terminal sequence. FEBS Lett., 312, 241-244.

142. P.J. Dolph, S.H. Man, S. Yarfitz, N.J. Colley, J.R. Deer, M. Spencer, J.B. Hurley, C.S. Zuker (1994). An eye-specific G beta subunit essential for termination of the phototransduction cascade. Nature, 370, 59-61.

143. Y. Hotta, S. Benzer (1970). Genetic dissection of the Drosophila nervous system by means of mosaics. Proc. Natl. Acad. Sci. U.S.A., 67, 1156-1163.

144. W.L. Pak, J. Grossfield, K.S. Arnold (1970). Mutants of the visual pathway of Drosophila melanogaster. Nature, 227, 518-520.

145. A. Fein, S. Cavar (2000). Divergent mechanisms for phototransduction of invertebrate microvillar photoreceptors. Vis. Neurosci., 17, 911-917.

146. F.H. Chen, A. Baumann, R. Payne, J.E. Lisman (2001). A cGMP-gated channel subunit in Limulus photoreceptors. Vis. Neurosci., 18, 517-526.

147. S. Chyb, P. Raghu, R.C. Hardie (1999). Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL. Nature, 397, 255-259.

148. P. Raghu, N.J. Colley, R. Webel, T. James, G. Hasan, M. Danin, Z. Selinger, R.C. Hardie (2000). Normal phototransduction in Drosophila photoreceptors lacking an InsP(3) receptor gene. Mol. Cell Neurosci., 15, 429-445.

149. C. Montell, G.M. Rubin (1989). Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron, 2, 1313-1323.

150. R.C. Hardie, B. Minke (1992). The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron, 8, 643-651.

151. A.M. Phillips, A. Bull, L.E. Kelly (1992). Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene. Neuron, 8, 631-642.

152. R.C. Hardie, B. Minke (1993). Novel Ca2+ channels underlying transduction in Drosophila photoreceptors: implications for phosphoinositide-mediated Ca2+ mobilization. Trends. Neurosci., 16, 371-376.

153. B.A. Niemeyer, E. Suzuki, K. Scott, K. Jalink, C.S. Zuker (1996). The Drosophila light-activated conductance is composed of the two channels TRP and TRPL. Cell, 85, 651-659.

154. A. Huber (2001). Scaffolding proteins organize multimolecular protein complexes for sensory signal transduction. Eur. J. Neurosci., 14, 769-776.

155. A. Huber, P. Sander, R. Paulsen (1996). Phosphorylation of the InaD gene product, a photoreceptor membrane protein required for recovery of visual excitation. J. Biol. Chem., 271, 11710-11717.

156. B.H. Shieh, M.Y. Zhu (1996). Regulation of the TRP Ca2+ channel by INAD in Drosophila photoreceptors. Neuron, 16, 991-998.

157. S. Tsunoda, J. Sierralta, Y. Sun, R. Bodner, E. Suzuki, A. Becker, M. Socolich, C.S. Zuker (1997). A multivalent PDZ-domain protein assembles signalling complexes in a G-protein-coupled cascade. Nature, 388, 243-249.

158. J. Chevesich, A.J. Kreuz, C. Montell (1997). Requirement for the PDZ domain protein, INAD, for localization of the TRP store-operated channel to a signaling complex. Neuron, 18, 95-105.

159. X.Z. Xu, A. Choudhury, X. Li, C. Montell (1998). Coordination of an array of signaling proteins through homo- and heteromeric interactions between PDZ domains and target proteins. J. Cell Biol., 142, 545-555.

160. A. Huber, P. Sander, A. Gobert, M. Bahner, R. Hermann, R. Paulsen (1996). The transient receptor potential protein (Trp), a putative store-operated Ca2+ channel essential for phosphoinositide-mediated photoreception, forms a signaling complex with NorpA, InaC and InaD. EMBO J., 15, 7036-7045.

161. X.Z. Xu, P.D. Wes, H. Chen, H.S. Li, M. Yu, S. Morgan, Y. Liu, C. Montell (1998). Retinal targets for calmodulin include proteins implicated in synaptic transmission. J. Biol. Chem., 273, 31297-31307.

162. M. Bahner, S. Frechter, N. Da Silva, B. Minke, R. Paulsen, A. Huber (2002). Light-regulated subcellular translocation of Drosophila TRPL channels induces long-term adaptation and modifies the light-induced current. Neuron, 34, 83 93.

163. M. Bahner, P. Sander, R. Paulsen, A. Huber (2000). The visual G protein of fly photoreceptors interacts with the PDZ domain assembled INAD signaling complex via direct binding of activated Galpha(q) to phospholipase cbeta. J. Biol. Chem., 275, 2901-2904.

164. R.C. Hardie, P. Raghu, S. Moore, M. Juusola, R.A. Baines, S.T. Sweeney (2001). Calcium influx via TRP channels is required to maintain PIP2 levels in Drosophila photoreceptors. Neuron, 30, 149-159.

165. S. Tsunoda, Y. Sun, E. Suzuki, C. Zuker (2000). Independent anchoring and assembly mechanisms of INAD signaling complexes in Drosophila photoreceptors. J. Neurosei. 21, 150-158.

166. H.S. Li, C. Montell (2000). TRP and the PDZ protein, INAD, form the core complex required for retention of the signalplex in Drosophila photoreceptor cells. J. Cell Biol., 150, 1411-1422.

167. A. Huber, G. Belusic, N. Da Silva, M. Bahner, G. Gerdon, K. Draslar, R. Paulsen (2000). The Calliphora rpa mutant lacks the PDZ domain-assembled INAD signalling complex. Eur. J. Neurosei., 12, 3909-3918.

168. M.P. Gomez, E. Nasi (2000). Light transduction in invertebrate hyperpolarizing photoreceptors: possible involvement of a Go-regulated guanylate cyclase. J. Neurosei., 20, 5254-5263.

169. M.P. Gomez, E. Nasi (1995). Activation of light-dependent K+ channels in ciliary invertebrate photoreceptors involves cGMP but not the IP3/Ca2+ cascade. Neuron, 15, 607-618.

170. D R. Hyde, K.L. Mecklenburg, J.A. Pollock, T.S. Vihtelic, S. Benzer (1990). Twenty Drosophila visual system cDNA clones: one is a homolog of human arrestin. Proe. Natl. Acad. Sci. U.S.A., 87, 1008-1012.

171. D.P. Smith, B.H. Shieh, C.S (1990). Zuker Isolation and structure of an arrestin gene from Drosophila. Proc. Natl. Acad. Sci. U.S.A., 87, 1003-1007.

172. H. LeVine, D.P. Smith, M. Whitney, D.M. Malicki, P.J. Dolph, G.F. Smith, W. Burkhart, C.S. Zuker (1990). Isolation of a novel visual-system-specific arrestin: an in vivo substrate for light-dependent phosphorylation. Mech. Dev., 33, 19-25.

173. T. Yamada, Y. Takeuchi, N. Komori, H. Kobayashi, Y. Sakai, Y. Hotta, H. Matsumoto (1990). A 49-kilodalton phosphoprotein in the Drosophila photoreceptor is an arrestin homolog. Science, 248, 483^486.

174. P.J. Dolph, R. Ranganathan, N.J. Colley, R.W. Hardy, M. Socolich, C.S. Zuker (1993). Arrestin function in inactivation of G protein-coupled receptor rhodopsin in vivo. Science, 260, 1910-1916.

175. P.G. Alloway, P.J. Dolph (1999). A role for the light-dependent phosphorylation of visual arrestin. Proc. Natl. Acad. Sci. U.S.A., 96, 6072-6077.

176. K. Hamdorf, S. Razmjoo (1977). The prolonged depolarizing afterpotential and its contribution to the understanding of photoreceptor function, Biophys. Struct. Meek, 3, 163-170.

177. W.L. Pak (1979). Study of photoreceptor function using Drosophila mutants. In: X.O. Breakfield (Ed.), Neurogenetics: Genetic Approaches to the Nervous System (pp. 67-99). Elsevier, North-Holland.

178. B. Minke (1986). Photopigment-dependent Adaptation in Invertebrates-Implication for Vertebrates. In: H. Stieve (ed.), The Molecular Mechanism of Photoreception (pp. 241-265). Springer-Verlag, Berlin.

179. K. Hamdorf, R. Paulsen, J. Schwemer (1989). Insect Photoreception: I. Primary Mechanisms of Visual Excitation. In: H.C. Liittgau, R. Necker (Eds), Biological Signal Processing (pp. 64-82). VCH Verlagsgemeinschaft, Weinheim.

180. H. Matsumoto, T. Yamada (1991). Phosrestins I and II: arrestin homologs which undergo differential light-induced phosphorylation in the Drosophila photoreceptor in vivo. Biochem. Biophys. Res. Commun., Ill, 1306-1312.

181. H. Matsumoto, B.T. Kurien, Y. Takagi, E.S. Kahn, T. Kinumi, N. Komori, T. Yamada, F. Hayashi, K. Isono, et al. (1994), Phosrestin I undergoes the earliest light-induced phosphorylation by a calcium/calmodulin-dependent protein kinase in Drosophila photoreceptors. Neuron, 12, 997-1010.

182. E.S. Kahn, H. Matsumoto (1997). Calcium/calmodulin-dependent kinase II phosphorylates Drosophila visual arrestin. J. Neurochem., 68, 169-175.

183. S.S. Ferguson, W.E. Downey, A.M. Colapietro, L.S. Barak, L. Menard, M.G. Caron (1996). Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization. Science, 271, 363-366.

184. O.B.J. Goodman, J.G. Krupnick, F. Santini, V.V. Gurevich, R.B. Penn, A.W. Gagnon, J.H. Keen, J.L. Benovic (1996). Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2- adrenergic receptor. Nature, 383, 447-450.

185. J. Zhang, S.S.G. Ferguson, L.S. Barak, L. Menard, M.G. Caron (1996). Dynamin and beta-arrestin reveal distinct mechanisms for G protein-coupled receptor internalization. J. Biol. Chem., 271, 18302-18305.

186. T. Byk, M. Bar-Yaacov, Y.N. Doza, B. Minke, Z. Selinger (1993). Regulatory arrestin cycle secures the fidelity and maintenance of the fly photoreceptor cell. Proc. Natl. Acad. Sci. U.S.A., 90, 1907-1911.

187. J. Vinos, K. Jalink, R.W. Hardy, S.G. Britt, C.S. Zuker (1997). A G proteincoupled receptor phosphatase required for rhodopsin function. Science, 277, 687-690.

188. W.C. Smith, R.M. Greenberg, B.G. Caiman, M.M. Hendrix, L. Hutchinson, L.A. Donoso, B.A. Battelle (1995). Isolation and expression of an arrestin cDNA from the horseshoe crab lateral eye. J. Neurochem., 64, 1-13.

189. J. Bentrop, M. Schillo, G. Gerdon, K. Draslar, R. Paulsen (2001). UV-light-dependent binding of a visual arrestin 1 isoform to photoreceptor membranes in a neuropteran (Ascalaphus) compound eye. FEBS Lett., 493, 112-116.

190. G. Berstein, J.L. Blank, D.Y. Jhon, J.H. Exton, S.G. Rhee, E.M. Ross (1992). Phospholipase C-beta 1 is a GTPase-activating protein for Gq/11, its physiologic regulator. Cell, 70, 411^118.

191. G.H. Biddlecome, G. Berstein, E.M. Ross (1996). Regulation of phospholipase C-beta 1 by Gq and ml muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. J. Biol. Chem., 271, 7999-8007.

192. B. Cook, M. Bar-Yaacov, B. Cohen, R.E. Goldstein, Z. Paroush, Z. Selinger, B. Minke (2000). Phospholipase C and termination of G-protein-mediated signalling in vivo. Nat. Cell Biol., 2, 296-301.

Chapter 3

Vertebrate rhodopsin

Oliver P. Ernst, Klaus Peter Hofmann and Krzysztof Palczewski

Table of contents

Abstract 79

3.1 Introduction 79

3.2 Phototransduction 80

3.2.1 The disk membrane 80

3.2.2 G-protein and the effector activation 82

3.2.3 Deactivation 83

3.3 Structure of bovine rhodopsin 83

3.3.1 Overall topology 84

3.3.2 The inactive ground state 88

3.4 Photoisomerization of rhodopsin 90

3.4.1 Classical photoisomerization pathway 90

3.4.2 Early events - storage of photon energy in bathorhodopsin 91

3.4.3 Relaxation and steric trigger - lumirhodopsin and metarhodopsin I 92

3.5 Metarhodopsin II: the active photoproduct of rhodopsin 93

3.5.1 Metarhodopsin II 93

3.5.2 Role of the hydrophobic environment and light-induced reorganization of disk membrane phospholipids 95

3.5.3 Formation of the signaling state 96

3.5.4 Mechanistic insights from archaeal rhodopsins and photoreversal of metarhodopsin II 97

3.6 Interaction between photoactivated rhodopsin and G-protein . . 99

3.6.1 Stabilization of metarhodopsin II by Gt 99

3.6.2 The rhodopsin-Gt interface 99 Binding sites at Gt 100 Binding sites at rhodopsin 100

3.6.3 Conclusions 101

3.7 Interactions between photoactivated rhodopsin and arrestin and rhodopsin kinase 102

3.7.1 Arrestin 102 Arrestin-receptor interaction sites 102 Conformational switch 103 Molecular recognition 104

3.7.2 Rhodopsin kinase 104 Signaling state 104 Interaction sites 105 Direct competition 105

3.8 Light-independent signaling of different forms of the apoprotein 106

3.8.2 Retinal-opsin complexes 106

3.9 Metabolism of retinal 107

Acknowledgements 109

References 109


Rhodopsin, described more than 120 years ago as the visual pigment of the retina, is a transmembrane protein composed of the apoprotein opsin and the covalently linked chromophore 11-m-retinal. It is highly expressed in rod cells, where it localizes to plasma and internal membranes of the rod outer segment, a specific cellular compartment dedicated for transformation of light energy into biochemical reactions. Absorption of light by the chromophore triggers transient conformational changes of the apoprotein, which in turn initiates the G-protein mediated enzymatic cascade of reactions, termed photo-transduction, that result in neuronal signaling. Rhodopsin is also the best-studied member of a large group of cell-surface receptors that signal through G-proteins and therefore are called G-protein-coupled receptors (GPCRs). Unique members of the GPCR superfamily are involved in a vast variety of specific cellular signal transduction processes including visual, taste and odor perceptions and sensing a variety of hormones. These receptors share a common seven-transmembrane a-helical structure and use the binding energy of extracellular chemical ligands for stabilization of an active receptor conformation. Thus, conformational changes of GPCRs allow transmission of the extracellular signal, across the plasma membrane, into the cell. Elucidation of the crystal structure of rhodopsin and characterization of fundamental aspects of the photoactivation mechanism paved the way for better understanding of other GPCRs. In this review, we describe the first steps in seeing, comprising light-induced activation of rhodopsin, and its interaction with proteins of the phototransduction cascade.

3.1 Introduction

In 1878, Kiihne and co-workers recognized that vision originates from the absorption of light by visual pigments [1,2]. These pigments are membrane-bound photoreceptor proteins composed of the apoprotein opsin and a retinal chromophore. In the retina of vertebrates, two main types of photoreceptor cells, rod and cone cells, are present. The rods are responsible for scotopic vision and several sub-types of cones for photopic vision. Rod visual pigment rhodopsin is a 40 kD integral membrane protein, which consists of the apoprotein opsin containing seven helices spanning the membrane and the prosthetic group 11-cw-retinal. The color of rhodopsin and its response to light arises from the covalent linkage of the 11-«¿-retinal chromophore. The chromophore is linked via a protonated Schiff base to Lys296 in helix VII, yielding a broad absorption with a maximum at 500 nm (e500 = 40,000 cm-1 M_1) that matches the solar spectrum. The human retina contains three sub-types of cone pigments that have distinct sensitivity to different wavelengths of visible light: blue, green and red pigments, with absorption maxima of 424, 530 and 560 nm, respectively [3], In principle, all visual pigments convert light energy into changes in the protein conformation, and in turn trigger intracellular reactions that ultimately lead to a neuronal impulse [4]. The prosthetic group that absorbs light (i.e. the chromophore) undergoes isomerization after photon absorption [5], and transmits the light energy to the chromophore-receptor complex, where it is initially stored as an energetically unfavorable conformation of the chromophore and an unstable tertiary conformation of the polypeptide chain. The signaling state of the receptor is then reached by a subsequent thermal relaxation process. The present chapter focusses on the most extensively studied visual pigment, rhodopsin.

Rod cells are capable of detecting single quanta [6], This ultimate sensitivity is achieved as a consequence of high probability of absorption of the incoming light, efficient photochemical reaction, a rapid, reproducible and greatly amplified intracellular signal transduction and a high signal-to-noise ratio of the overall transduction process. The visual system evolved just to perform such a task. A prerequisite of such signaling properties is for rhodopsin to have an extremely low dark activity. In the time domain of the electrical response, no spontaneous activation is tolerated from any of the 108 inactive rhodopsin molecules present in a photoreceptor cell. The estimated lifetime of the inactive state of rhodopsin is >10 years (see e.g. [4]). However, when rhodopsin is photoactivated, it initiates the transduction cascade with maximal quantum efficiency.

The phototransduction system is composed of the G-protein transducin (Gt), named according to its rod cell-specific expression of the a-subunit, and the effector, a cGMP-specific phoshodiesterase (reviewed in [7]). Therefore, rhodopsin is considered to be a member of a large group of transmembrane proteins of similar topology, termed G-protein-coupled receptors (GPCRs). Upon activation of GPCRs by ligand binding, or in the case of visual pigments by photon-induced alteration in the conformation of the bound ligand, the cytoplasmic surface of GPCRs becomes competent for G-protein binding, leading to subsequent catalytic GDP/GTP exchange on the a-subunit and G-protein activation. In general, GPCRs serve to respond to chemical signals and transmit them across biological membranes by coupling to heterotrimeric guanine nucleotide-binding proteins (G-proteins), which in turn, modulate effector protein activity and thereby affect second messenger levels (reviewed by [8]).

Was this article helpful?

0 0

Post a comment