ACKNOWLEDGMENTS

We wish to thank J. Pfannstiel and I. Huber for critical comments on the manuscript. Our work is supported by grants from the Deutsche Forschungsgemeinschaft (Hu 839/2-4), the German-Israel-Foundation (GIF), and the Hertie-Foundation.

REFERENCES

1.Lamb, T. D. (1996). Gain and kinetics of activation in the G-protein cascade of phototransduction. Proc. Natl. Acad. Sci. U. S. A. 93, 566–570.

2.Stryer, L. (1986). Cyclic GMP cascade of vision. Annu. Rev. Neurosci. 9, 87–119.

3.Hardie, R. C., Raghu, P. (2001). Visual transduction in Drosophila. Nature 413, 186–193.

4.Montell, C. (1999). Visual transduction in Drosophila. Annu. Rev. Cell Dev. Biol. 15, 231–268.

5.Koutalos, Y., Yau, K. W. (1996). Regulation of sensitivity in vertebrate rod photoreceptors by calcium. Trends Neurosci. 19, 73–81.

6.Wu, C. F., Pak, W. L. (1975). Quantal basis of photoreceptor spectral sensitivity of Drosophila melanogaster. J. Gen. Physiol. 66, 149–168.

7.Baylor, D. A., Lamb, T. D., Yau, K. W. (1979). Responses of retinal rods to single photons. J. Physiol. 288, 613–634.

8.Tsunoda, S., Sierralta, J., Zuker, C. S. (1998). Specificity in signaling pathways: assembly into multimolecular signaling complexes. Curr. Opin. Genet. Dev. 8, 419–422.

9.Ranganathan, R., Harris, G. L., Stevens, C. F., Zuker, C. S. (1991). A Drosophila mutant defective in extracellular calcium-dependent photoreceptor deactivation and rapid desensitization. Nature 354, 230–232.

10.Zuker, C. S. (1996). The biology of vision of Drosophila. Proc. Natl. Acad. Sci. U. S. A. 93, 571–576.

11.Minke, B., Parnas, M. (2006). Insights on TRP channels from in vivo studies in Drosophila. Annu. Rev. Physiol. 68, 649–684.

12.Minke, B., Hardie, R. C. (2000). Genetic dissection of Drosophila phototransduction. In: Handbook of biological physics, Volume 3: molecular mechanisms in visual transduction (Stavenga, D., DeGrip, W. J., Pugh, E. N., Jr., eds.), pp. 449–525. Elsevier, Amsterdam.

13.Pak, W. L., Leung, H. T. (2003). Genetic approaches to visual transduction in Drosophila melanogaster. Receptors Channels 9, 149–167.

14.Minke, B., Cook, B. (2002). TRP channel proteins and signal transduction. Physiol. Rev. 82, 429–472.

15.Paulsen, R., Bähner, M., Huber, A., Schillo, M., Schulz, S., Wottrich, R., Bentrop, J. (2001). The molecular design of a visual cascade: Molecular stages of phototransduction in Drosophila. In: Vision: the approach of biophysics and neurosciences (Musio, C., ed.), pp. 41–59. World Scientific, Singapore.

16.Tsunoda, S., Zuker, C. S. (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.

17.Paulsen, R., Bähner, M., Bentrop, J., Schillo, M., Schulz, S., Huber, A. (2001). The molecular design of a visual cascade: assembly of the Drosophila phototransduction pathway into a supramolecular signaling complex. In: Vision: the approach of biophysics and neurosciences (Musio, C., ed.), pp. 60–73. World Scientific, Singapore.

18.Montell, C. (1998). TRP trapped in fly signaling web. Curr. Opin. Neurobiol. 8, 389–397.

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

20.Ranganathan, R., Ross, E. M. (1997). PDZ domain proteins: scaffolds for signaling complexes. Curr. Biol. 7, R770–R773.

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

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

23.Gehring, W. J. (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.

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

25.Bentrop, J., Paulsen, R. (2003). Invertebrate rhodopsins. In: Photoreceptors and light signalling (Batschauer, A., ed.), pp. 40–76. Royal Society of Chemistry, Cambridge, UK.

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

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

28.Pak, W. L. (1979). Study of photoreceptor function using Drosophila mutants. In: Neurogenetics: genetic approaches to the nervous system (Breakefield, X., ed.), pp. 67–99. Elsevier, Amsterdam.

29.Bloomquist, B. T., Shortridge, R. D., Schneuwly, S., Perdew, 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.

30.Shieh, B. H., Niemeyer, B. (1995). A novel protein encoded by the InaD gene regulates recovery of visual transduction in Drosophila. Neuron 14, 201–210.

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

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

33.Huber, A., Sander, P., Gobert, A., Bahner, M., Hermann, R., Paulsen, R. (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.

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

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

36.Wes, P. D., Xu, X. Z., Li, H. S., Chien, F., Doberstein, S. K., Montell, C. (1999). Termination of phototransduction requires binding of the NINAC myosin III and the PDZ protein INAD. Nat. Neurosci. 2, 447–453.

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

38.Doyle, D. A., Lee, A., Lewis, J., Kim, E., Sheng, M., MacKinnon, R. (1996). Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85, 1067–1076.

39.Morais-Cabral, J. H., Petosa, C., Sutcliffe, M. J., Raza, S., Byron, O., Poy, F., Marfatia, S. M., Chishti, A. H., Liddington, R. C. (1996). Crystal structure of a PDZ domain. Nature 382, 649–652.

40.Hung, A. Y., Sheng, M. (2002). PDZ domains: structural modules for protein complex assembly. J. Biol. Chem. 277, 5699–5702.

41.Harris, B. Z., Lim, W. A. (2001). Mechanism and role of PDZ domains in signaling complex assembly. J. Cell Sci. 114, 3219–3231.

42.Songyang, Z., Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A., Chan, A. C., Anderson, J. M., Cantley, L. C. (1997). Recognition of unique carboxyl-termi- nal motifs by distinct PDZ domains. Science 275, 73–77.

43.Stricker, N. L., Christopherson, K. S., Yi, B. A., Schatz, P. J., Raab, R. W., Dawes, G., Bassett, D. E., Jr., Bredt, D. S., Li, M. (1997). PDZ domain of neuronal nitric oxide synthase recognizes novel C-terminal peptide sequences. Nat. Biotechnol. 15, 336–342.

44.Maximov, A., Sudhof, T. C., Bezprozvanny, I. (1999). Association of neuronal calcium channels with modular adaptor proteins. J. Biol. Chem. 274, 24453–24456.

45.Kimple, M. E., Siderovski, D. P., Sondek, J. (2001). Functional relevance of the disulfide-linked complex of the N-terminal PDZ domain of InaD with NorpA. EMBO J. 20, 4414–4422.

46.Adamski, F. M., Zhu, M. Y., Bahiraei, F., Shieh, B. H. (1998). Interaction of eye protein kinase C and INAD in Drosophila. Localization of binding domains and electrophysiological characterization of a loss of association in transgenic flies. J. Biol. Chem. 273, 17713– 17719.

47.van Huizen, R., Miller, K., Chen, D. M., Li, Y., Lai, Z. C., Raab, R. W., Stark, W. S., Shortridge, R. D., Li, M. (1998). Two distantly positioned PDZ domains mediate multivalent INADphospholipase C interactions essential for G protein-coupled signaling. EMBO J. 17, 2285–2297.

48.Georgiev, P., Garcia-Murillas, I., Ulahannan, D., Hardie, R. C., Raghu, P. (2005). Functional INAD complexes are required to mediate degeneration in photoreceptors of the Drosophila rdgA mutant. J. Cell Sci. 118, 1373–1384.

49.Li, H. S., Montell, C. (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, 1411–1421.

50.Tsunoda, S., Sun, Y., Suzuki, E., Zuker, C. (2001). Independent anchoring and assembly mechanisms of INAD signaling complexes in Drosophila photoreceptors. J. Neurosci. 21, 150–158.

51.Chorna-Ornan, I., Tzarfaty, V., Ankri-Eliahoo, G., Joel-Almagor, T., Meyer, N. E., Huber, A., Payre, F., Minke, B. (2005). Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors. J. Cell Biol. 171, 143–152.

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

53.Yarfitz, S. L., Running, D. J., Froelick, G., Colley, N. J., Hurley, J. B. (1994). In situ assay of light-stimulated G protein activity in Drosophila photoreceptor G protein beta mutants. J. Biol. Chem. 269, 30340–30344.

54.Kosloff, M., Elia, N., Joel-Almagor, T., Timberg, R., Zars, T. D., Hyde, D. R., Minke, B., Selinger, Z. (2003). Regulation of light-dependent Gq alpha translocation and morphological changes in fly photoreceptors. EMBO J. 22, 459–468.

55.Cronin, M. A., Diao, F., Tsunoda, S. (2004). Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. J. Cell Sci. 117, 4797–4806.

56.Lee, S. J., Xu, H., Kang, L. W., Amzel, L. M., Montell, C. (2003). Light adaptation through phosphoinositide-regulated translocation of Drosophila visual arrestin. Neuron 39, 121–132.

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

58.Shieh, B. H., Zhu, M. Y., Lee, J. K., Kelly, I. M., Bahiraei, F. (1997). Association of INAD with NORPA is essential for controlled activation and deactivation of Drosophila phototransduction in vivo. Proc. Natl. Acad. Sci. U. S. A. 94, 12682–12687.

59.Henderson, S. R., Reuss, H., Hardie, R. C. (2000). Single photon responses in Drosophila photoreceptors and their regulation by Ca2+. J. Physiol. (Lond.) 524, 179–194.

60.Huber, A., Sander, P., Bahner, M., Paulsen, R. (1998). The TRP Ca2+ channel assembled in a signaling complex by the PDZ domain protein INAD is phosphorylated through the interaction with protein kinase C (ePKC). FEBS Lett. 425, 317–322.

61.Liu, M., Parker, L. L., Wadzinski, B. E., Shieh, B. H. (2000). Reversible phosphorylation of the signal transduction complex in Drosophila photoreceptors. J. Biol. Chem. 275, 12194–12199.

62.Popescu, D. C., Ham, A. J., Shieh, B. H. (2006). Scaffolding protein INAD regulates deactivation of vision by promoting phosphorylation of transient receptor potential by eye protein kinase C in Drosophila. J. Neurosci. 26, 8570–8577.

63.Bähner, M., Sander, P., Paulsen, R., Huber, A. (2000). The visual G protein of fly photore-

ceptors interacts with the PDZ domain assembled INAD signaling complex via direct binding of activated Gαq to phospholipase Cβ. J. Biol. Chem. 275, 2901–2904.

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

65.Scott, K., Zuker, C. S. (1998). Assembly of the Drosophila phototransduction cascade into a signalling complex shapes elementary responses. Nature 395, 805–808.

66.Hardie, R. C., Martin, F., Cochrane, G. W., Juusola, M., Georgiev, P., Raghu, P. (2002). Molecular basis of amplification in Drosophila phototransduction: Roles for G protein, phospholipase C, and diacylglycerol kinase. Neuron 36, 689–701.

67.Baylor, D. A., Matthews, G., Yau, K. W. (1980). Two components of electrical dark noise in toad retinal rod outer segments. J. Physiol. 309, 591–621.

68.Elia, N., Frechter, S., Gedi, Y., Minke, B., Selinger, Z. (2005). Excess of Gβe over Gqαe in vivo prevents dark, spontaneous activity of Drosophila photoreceptors. J. Cell Biol. 171, 517–526.

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

70.Molday, R. S. (1996). Calmodulin regulation of cyclic-nucleotide-gated channels. Curr. Opin. Neurobiol. 6, 445–452.

71.Körschen, H. G., Beyermann, M., Muller, F., Heck, M., Vantler, M., Koch, K. W., Kellner, R., Wolfrum, U., Bode, C., Hofmann, K. P., Kaupp, U. B. (1999). Interaction of glutamic- acid-rich proteins with the cGMP signalling pathway in rod photoreceptors. Nature 400, 761–766.

72.Poetsch, A., Molday, L. L., Molday, R. S. (2001). The cGMP-gated channel and related glutamic acid-rich proteins interact with peripherin-2 at the rim region of rod photoreceptor disc membranes. J. Biol. Chem. 276, 48009–48016.

73.Molday, R. S., Molday, L. L. (1998). Molecular properties of the cGMP-gated channel of rod photoreceptors. Vision Res. 38, 1315–1323.

74.Bauer, P. J., Drechsler, M. (1992). Association of cyclic GMP-gated channels and Na(+)- Ca(2+)-K+ exchangers in bovine retinal rod outer segment plasma membranes. J. Physiol. 451, 109–131.

75.Schwarzer, A., Kim, T. S., Hagen, V., Molday, R. S., Bauer, P. J. (1997). The Na/Ca-K exchanger of rod photoreceptor exists as dimer in the plasma membrane. Biochemistry. 36, 13667–13676.

76.Schwarzer, A., Schauf, H., Bauer, P. J. (2000). Binding of the cGMP-gated channel to the Na/Ca-K exchanger in rod photoreceptors. J. Biol. Chem. 275, 13448–13454.

77.Boesze-Battaglia, K., Lamba, O. P., Napoli, A. A., Jr., Sinha, S., Guo, Y. (1998). Fusion between retinal rod outer segment membranes and model membranes: a role for photoreceptor peripherin/rds. Biochemistry 37, 9477–9487.