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Journal of Molecular Evolution

, Volume 59, Issue 2, pp 204–217 | Cite as

Diversity of Guanylate Cyclase-Activating Proteins (GCAPs) in Teleost Fish: Characterization of Three Novel GCAPs (GCAP4, GCAP5, GCAP7) from Zebrafish (Danio rerio) and Prediction of Eight GCAPs (GCAP1-8) in Pufferfish (Fugu rubripes)

  • Yoshikazu Imanishi
  • Lili Yang
  • Izabela Sokal
  • Sławomir Filipek
  • Krzysztof Palczewski
  • Wolfgang Baehr
Articles

Abstract

The guanylate cyclase-activating proteins (GCAPs) are Ca2+-binding proteins of the calmodulin (CaM) gene superfamily that function in the regulation of photoreceptor guanylate cyclases (GCs). In the mammalian retina, two GCAPs (GCAP 1-2) and two transmembrane GCs have been identified as part of a complex regulatory system responsive to fluctuating levels of free Ca2+. A third GCAP, GCAP3, is expressed in human and zebrafish (Danio rerio) retinas, and a guanylate cyclase-inhibitory protein (GCIP) has been shown to be present in frog cones. To explore the diversity of GCAPs in more detail, we searched the pufferfish (Fugu rubripes) and zebrafish (Danio rerio) genomes for GCAP-related gene sequences (fuGCAPs and zGCAPs, respectively) and found that at least five additional GCAPs (GCAP4-8) are predicted to be present in these species. We identified genomic contigs encoding fuGCAPl-8, fuGCIP, zGCAPl-5, zGCAP7 and zGCIP. We describe cloning, expression and localization of three novel GCAPs present in the zebrafish retina (zGCAP4, zGCAP5, and zGCAP7). The results show that recombinant zGCAP4 stimulated bovine rod outer segment GC in a Ca2+-dependent manner. RT-PCR with zGCAP specific primers showed specific expression of zGCAPs and zGCIP in the retina, while zGCAPl mRNA is also present in the brain. In situ hybridization with anti-sense zGCAP4, zGCAP5 and zGCAP7 RNA showed exclusive expression in zebrafish cone photoreceptors. The presence of at least eight GCAP genes suggests an unexpected diversity within this subfamily of Ca2+-binding proteins in the teleost retina, and suggests additional functions for GCAPs apart from stimulation of GC. Based on genome searches and EST analyses, the mouse and human genomes do not harbor GCAP4-8 or GCIP genes.

Keywords

Guanylate cyclase Guanylate cyclase-activating proteins Phototransduction Ca2+-binding proteins Rod and cone photoreceptors 

Notes

Acknowledgments

We would like to thank Darin Bronson for expert technical assistance with this project. This research was supported by grants from the NIH (EY08123, to W.B., and EY08061, to K.P.), the Ruth and Milton Steinbach Fund, the E.k. Bishop Foundation, the Alcon Research Institute, and Research to Prevent Blindness, Inc. (RPB), to the Departments of Ophthalmology at the University of Washington and the University of Utah, and a Center Grant from Foundation Fighting Blindness, Inc., to the University of Utah. W.B. and K.P. are recipients of an RPB Senior Investigator Award. W.B. acknowledges an endowment from Ralph and Mary Tuck to the Department of Ophthalmology at the University of Utah.

References

  1. Altschul, SF, Gish, W, Miller, W, Myers, EW, Lipman, DJ 1990Basic local alignment search toolJ Mol Biol215403410CrossRefPubMedGoogle Scholar
  2. Ames, JB, Dizhoor, AM, Ikura, M, Palczewski, K, Stryer, L 1999Three-dimensional structure of guanylyl cyclase activating protein-2, a calcium-sensitive modulator of photoreceptor guanylyl cyclasesJ Biol Chem2741932919337PubMedGoogle Scholar
  3. Aparicio, S, Chapman, J, Stupka, E, Putnam, N, Chia, JM, Dehal, P, Christoffels, A, Rash, S, Hoon, S, Smit, A, Gelpke, MD, Roach, J, Oh, T, Ho, IY, Wong, M, Detter, C, Verhoef, F, Predki, P, Tay, A, Lucas, S, Richardson, P, Smith, SF, Clark, MS, Edwards, YJ, Doggett, N, Zharkikh, A, Tavtigian, SV, Pruss, D, Barnstead, M, Evans, C, Baden, H, Powell, J, Glusman, G, Rowen, L, Hood, L, Tan, YH, Elgar, G, Hawkins, T, Venkatesh, B, Rokhsar, D, Brenner, S 2002Whole-genome shotgun assembly and analysis of the genome of Fugu rubripesScience29713011310CrossRefPubMedGoogle Scholar
  4. Applebury, ML, Antoch, MP, Baxter, LC, Chun, LL, Falk, JD, Farhangfar, F, Kage, K, Krzystolik, MG, Lyass, LA, Robbins, JT 2000The murine cone photoreceptor: A single cone type expresses both S and M opsins with retinal spatial patterningNeuron27513523PubMedGoogle Scholar
  5. Asaoka, Y, Mano, H, Kojima, D, Fukada, Y 2002Pineal expression-promoting element (PIPE), a cis-acting element, directs pineal-specific gene expression in zebrafishProc Natl Acad Sci USA991545615461PubMedGoogle Scholar
  6. Branchek, T, Bremiller, R 1984The development of photoreceptors in the zebrafish, Brachydanio rerio I. StructureJ Comp Neurol224107115PubMedGoogle Scholar
  7. Chinen, A, Hamaoka, T, Yamada, Y, Kawamura, S 2003Gene duplication and spectral diversification of cone visual pigments of zebrafishGenetics163663675PubMedGoogle Scholar
  8. Cuenca, N, Lopez, S, Howes, K, Kolb, H 1998The localization of guanylyl cyclase-activating proteins in the mammalian retinaInvest Ophthalmol Vis Sci3912431250PubMedGoogle Scholar
  9. Dizhoor, AM, Lowe, DG, Olshevskaya, EV, Laura, RP, Hurley, JB 1994The human photoreceptor membrane guanylyl cyclase, RetGC, is present in outer segments and is regulated by calcium and a soluble activatorNeuron1213451352PubMedGoogle Scholar
  10. Dizhoor, AM, Olshevskaya, EV, Henzel, WJ, Wong, SC, Stults, JT, Ankoudinova, I, Hurley, JB 1995Cloning, sequencing, and expression of a 24-kDa Ca2+-binding protein activating photoreceptor guanylyl cyclaseJ Biol Chem2702520025206PubMedGoogle Scholar
  11. Felsenstein, J 2002PHYLIP (phylogeny inference package), version 3.6. Distributed by the author, Department of GeneticsUniversity of WashingtonSeattleGoogle Scholar
  12. Garbers, DL, Lowe, DG 1994Guanylyl cyclase receptorsJ Biol Chem2693074130744PubMedGoogle Scholar
  13. Gorczyca, WA, Gray-Keller, MP, Detwiler, PB, Palczewski, K 1994Purification and physiological evaluation of a guanylate cyclase activating protein from retinal rodsProc Natl Acad Sci USA9140144018PubMedGoogle Scholar
  14. Gorczyca, WA, Polans, AS, Surgucheva, I, Subbaraya, I, Baehr, W, Palczewski, K 1995Guanylyl cyclase activating protein: A calcium-sensitive regulator of phototransductionJ Biol Chem2702202922036PubMedGoogle Scholar
  15. Haeseleer, F, Sokal, I, Li, N, Pettenati, M, Rao, N, Bronson, D, Wechter, R, Baehr, W, Palczewski, K 1999Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamilyJ Biol Chem27465266535CrossRefPubMedGoogle Scholar
  16. Harumi, T, Watanabe, T, Yamamoto, T, Tanabe, Y, Suzuki, N 2003Expression of membrane-bound and soluble guanylyl cyclase mRNAs in embryonic and adult retina of the medaka fish Oryzias latipesZool Sci20133140PubMedGoogle Scholar
  17. Hisatomi, O, Honkawa, H, Imanishi, Y, Satoh, T, Tokunaga, F 1999Three kinds of guanylate cyclase expressed in medaka photoreceptor cells in both retina and pineal organBiochem Biophys Res Commun255216220PubMedGoogle Scholar
  18. Howes, K, Bronson, JD, Dang, YL, Li, N, Zhang, K, Ruiz, C, Helekar, B, Lee, M, Subbaraya, I, Kolb, H, Chen, J, Baehr, W 1998Gene array and expression of mouse retina guanylate cyclase activating proteins 1 and 2Invest Ophthalmol Vis Sci39867875PubMedGoogle Scholar
  19. Howes, KA, Pennesi, ME, Sokal, I, Church-Kopish, J, Schmidt, B, Margolis, P, Frederick, J, Rieke, F, Palczewski, K, Wu, SM, Detwiler, PB, Baehr, W 2002GCAP1 rescues rod photoreceptor response in GCAP1/GCAP2 knockout miceEMBO J2115451554CrossRefPubMedGoogle Scholar
  20. Imanishi, Y, Li, N, Sowa, ME, Lichtarge, O, Wensel, TG, Saperstein, DA, Baehr, W, Palczewski, K 2002Characterization of retinal guanylate cyclase-activating protein 3 (GCAP3) from zebrafish to manEur J Neurosci156378PubMedGoogle Scholar
  21. Kachi, S, Nishizawa, Y, Olshevskaya, E, Yamazaki, A, Miyake, Y, Wakabayashi, T, Dizhoor, A, Usukura, J 1999Detailed localization of photoreceptor guanylate cyclase activating protein-1 and –2 in mammalian retinas using light and electron microscopyExp Eye Res68465473CrossRefPubMedGoogle Scholar
  22. Kainz, PM, Adolph, AR, Wong, KY, Dowling, JE 2003Lazy eyes zebrafish mutation affects Muller glial cells, compromising photoreceptor function and causing partial blindnessJ Comp Neurol463265280PubMedGoogle Scholar
  23. Kusakabe, T, Suzuki, N 2001A cis-regulatory element essential for photoreceptor cell-specific expression of a medaka retinal guanylyl cyclase geneDev Genes Evol211145149PubMedGoogle Scholar
  24. Li, N, Fariss, RN, Zhang, K, Otto-Bruc, A, Haeseleer, F, Bronson, JD, Qin, N, Yamazaki, A, Subbaraya, I, Milam, AH, Palczewski, K, Baehr, W 1998Guanylate cyclase inhibitory protein is a frog retinal Ca2+ binding protein related to mammalian guanylate cyclase activating proteinsEur J Biochem252591599PubMedGoogle Scholar
  25. Li, N, Sokal, I, Bronson, JD, Palczewski, K, Baehr, W 2001Identification and functional regions of guanylate cyclase-activating protein 1 (GCAP1) using GCAP1/GCIP chimerasBiol Chem38211791188PubMedGoogle Scholar
  26. Lichtarge, O, Bourne, HR, Cohen, FE 1996Evolutionary conserved Gαβγ binding surfaces support a model of the G protein-receptor complexProc Natl Acad Sci USA9375077511CrossRefPubMedGoogle Scholar
  27. Lowe, DG, Dizhoor, AM, Liu, K, Gu, Q, Spencer, M, Laura, R, Lu, L, Hurley, JB 1995Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2Proc Natl Acad Sci USA9255355539PubMedGoogle Scholar
  28. Maeda, T, Maeda, A, Maruyama, I, Ogawa, KI, Kuroki, Y, Sahara, H, Sato, N, Ohguro, H 2001Mechanisms of photoreceptor cell death in cancer-associated retinopathyInvest Ophthalmol Vis Sci42705712PubMedGoogle Scholar
  29. Malicki, J 2000Harnessing the power of forward genetics—Analysis of neuronal diversity and patterning in the zebrafish retinaTrends Neurosci23531541PubMedGoogle Scholar
  30. Marc, RE, Cameron, D 2001A molecular phenotype atlas of the zebrafish retinaJ Neurocytol30593654PubMedGoogle Scholar
  31. McBee, JK, Palczewski, K, Baehr, W, Pepperberg, DR 2001Confronting complexity: The interlink of phototransduction and retinoid metabolism in the vertebrate retinaProg Retin Eye Res20469529PubMedGoogle Scholar
  32. Mendez, A, Burns, ME, Sokal, I, Dizhoor, AM, Baehr, W, Palczewski, K, Baylor, DA, Chen, J 2001Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensititvity of rod photoreceptorsProc Natl Acad Sci USA9899489953PubMedGoogle Scholar
  33. Newbold, RJ, Deery, EC, Walker, CE, Wilkie, SE, Srinivasan, N, Hunt, DM, Bhattacharya, SS, Warren, MJ 2001The destabilization of human GCAP1 by a proline to leucine mutation might cause cone-rod dystrophyHum Mol Genet104754PubMedGoogle Scholar
  34. Notredame, C, Higgins, DG, Heringa, J 2000T-Coffee: A novel method for fast and accurate multiple sequence alignmentJ Mol Biol302205217CrossRefPubMedGoogle Scholar
  35. Olshevskaya, EV, Boikov, S, Ermilov, A, Krylov, D, Hurley, JB, Dizhoor, AM 1999Mapping functional domains of the guanylate cyclase regulator protein, GCAP-2J Biol Chem2741082310832PubMedGoogle Scholar
  36. Otto-Bruc, A, Buczylko, J, Surgucheva, I, Subbaraya, I, Rudnicka-Nawrot, M, Crabb, J, Arendt, A, HArgrave, PA, Baehr, W, Palczewski, K 1997aFunctional reconstitution of photoreceptor guanylate cyclase with native and mutant forms of guanylate cyclase activating protein 1Biochemistry3642954302Google Scholar
  37. Otto-Bruc, A, Fariss, RN, Haeseleer, F, Huang, J, Buczylko, J, Surgucheva, I, Baehr, W, Milam, AH, Palczewski, K 1997bLocalization of guanylate cyclase activating protein 2 in mammalian retinasProc Natl Acad Sci USA9447274732Google Scholar
  38. Palczewski, K, Subbaraya, I, Gorczyca, WA, Helekar, BS, Ruiz, CC, Ohguro, H, Huang, J, Zhao, X, Crabb, JW, Johnson, RS, Walsh, KA, Gray-Keller, MP, Detwiler, PB, Baehr, W 1994Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase activating protein (GCAP)Neuron13395404CrossRefPubMedGoogle Scholar
  39. Palczewski, K, Polans, AS, Baehr, W, Ames, JB 2000Calcium binding proteins in the retina: Structure, function, and the etiology of human visual diseasesBioEssays22337350PubMedGoogle Scholar
  40. Papermaster, DS 1982Preparation of retinal rod outer segmentsMethods Enzymol814852PubMedGoogle Scholar
  41. Payne, AM, Downes, SM, Bessant, DA, Taylor, R, Holder, GE, Warren, MJ, Bird, AC, Bhattacharya, SS 1998A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1Hum Mol Genet7273277CrossRefPubMedGoogle Scholar
  42. Payne, AM, Downes, SM, Bessant, DA, Plant, C, Moore, T, Bird, AC, Bhattacharya, SS 1999Genetic analysis of the guanylate cyclase activator IB (GUCA1B) gene in patients with autosomal dominant retinal dystrophiesJ Med Genet36691693PubMedGoogle Scholar
  43. Pennesi, ME, Howes, KA, Baehr, W, Wu, SM 2003GCAP1 rescues normal cone photoreceptor responses in GCAP1/GCAP2 knockout miceProc Natl Acad Sci USA10067836788PubMedGoogle Scholar
  44. Polans, A, Baehr, W, Palczewski, K 1996Turned on by Ca2+ ! The physiology and pathology of Ca2+ binding proteins in the retinaTrends Neurosci19547554PubMedGoogle Scholar
  45. Raymond, PA, Barthel, LK, Rounsifer, ME, Sullivan, SA, Knight, JK 1993Expression of rod and cone visual pigments in goldfish and zebrafish: A rhodopsin-like gene is expressed in conesNeuron1011611174PubMedGoogle Scholar
  46. Raz, E 2003Primordial germ-cell development: The zebrafish perspectiveNat Rev Genet4690700PubMedGoogle Scholar
  47. Schoenmakers, TJ, Visser, GJ, Flik, G, Theuvenet, AP 1992CHELATOR: An improved method for computing metal ion concentrations in physiological solutionsBiotechniques12870879PubMedGoogle Scholar
  48. Seimiya, M, Kusakabe, T, Suzuki, N 1997Primary structure and differential gene expression of three membrane forms of guanylyl cyclase found in the eye of the teleost Oryzias latipesJ Biol Chem2722340723417PubMedGoogle Scholar
  49. Semple-Rowland, SL, Larkin, P, Bronson, JD, Nykamp, K, Streit, WJ, Baehr, W 1999Characterization of the chicken GCAP gene array and analyses of GCAP1, GCAP2, and GC1 gene expression in normal and rd chicken pinealMol Vis514PubMedGoogle Scholar
  50. Shyjan, AW, Sauvage, FJ, Gillett, NA, Goeddel, DV, Lowe, DG 1992Molecular cloning of a retina-specific membrane guanylyl cyclaseNeuron9727737PubMedGoogle Scholar
  51. Sokal, I, Li, N, Surgucheva, I, Warren, MJ, Payne, AM, Bhattacharya, SS, Baehr, W, Palczewski, K 1998GCAP1(Y99C) mutant is constitutively active in autosomal dominant cone dystrophyMol Cell2129133CrossRefPubMedGoogle Scholar
  52. Sokal, I, Otto-Bruc, AE, Surgucheva, I, Verlinde, CL, Wang, CK, Baehr, W, Palczewski, K 1999Conformational changes in guanylyl cyclase-activating protein 1 (GCAP1) and its tryptophan mutants as a function of calcium concentrationJ Biol Chem2741982919837PubMedGoogle Scholar
  53. Sokal, I, Li, N, Verlinde, CL, Haeseleer, F, Baehr, W, Palczewski, K 2000Ca2+-binding proteins in the retina: from discovery to etiology of human disease(1)Biochim Biophys Acta1498233251PubMedGoogle Scholar
  54. Sokal, I, Li, N, Klug, CS, Filipek, S, Hubbell, WL, Baehr, W, Palczewski, K 2001Calcium-sensitive regions of GCAP1 as observed by chemical modifications, fluorescence and EPR spectroscopiesJ Biol Chem2764336143373PubMedGoogle Scholar
  55. Subbaraya, I, Ruiz, CC, Helekar, BS, Zhao, X, Gorczyca, WA, Pettenati, MJ, Rao, PN, Palczewski, K, Baehr, W 1994Molecular characterization of human and mouse photoreceptor guanylate cyclase activating protein (GCAP) and chromosomal localization of the human geneJ Biol Chem2693108031089PubMedGoogle Scholar
  56. Surguchov, A, Bronson, JD, Banerjee, P, Knowles, JA, Ruiz, CC, Subbaraya, I, Palczewski, K, Baehr, W 1997The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on the short arm of chromosome 6 (p21.1)Genomics39312322PubMedGoogle Scholar
  57. Tohya, S, Mochizuki, A, Iwasa, Y 2003Difference in the retinal cone mosaic pattern between zebrafish and medaka: cell-rearrangement modelJ Theor Biol221289300PubMedGoogle Scholar
  58. Venkatesh, B, Gilligan, P, Brenner, S 2000Fugu: A compact vertebrate reference genomeFEBS Lett47637PubMedGoogle Scholar
  59. Vihtelic, TS, Doro, CJ, Hyde, DR 1999Cloning and characterization of six zebrafish photoreceptor opsin cDNAs and immunolocalization of their corresponding proteinsVis Neurosci16571585PubMedGoogle Scholar
  60. Wilkie, SE, Stinton, I, Cottrill, P, Deery, E, Newbold, R, Warren, MJ, Bhattacharya, SS, Hunt, DM 2002Characterisation of two genes for guanylate cyclase activator protein (GCAP1 and GCAP2) in the Japanese pufferfish, Fugu rubripesBiochim Biophys Acta15777380PubMedGoogle Scholar
  61. Wilkie, SE, Li, Y, Deery, EC, Newbold, RJ, Garibaldi, D, Bateman, JB, Zhang, H, Lin, W, Zack, DJ, Bhattacharya, SS, Warren, MJ, Hunt, DM, Zhang, K 2001Identification and functional consequences of a new mutation (E155G) in the gene for GCAP1 that causes autosomal dominant cone dystrophyAm J Hum Genet69471480CrossRefPubMedGoogle Scholar
  62. Wittbrodt, J, Shima, A, Schartl, M 2002Medaka—A model organism from the far EastNat Rev Genet35364PubMedGoogle Scholar
  63. Yang, RB, Garbers, DL 1997Two eye guanylyl cyclases are expressed in the same photoreceptor cells and form homomers in preference to heteromersJ Biol Chem2721373813742PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Yoshikazu Imanishi
    • 1
  • Lili Yang
    • 2
  • Izabela Sokal
    • 1
  • Sławomir Filipek
    • 3
  • Krzysztof Palczewski
    • 1
    • 4
    • 5
  • Wolfgang Baehr
    • 2
    • 6
    • 7
  1. 1.Department of OphthalmologyUniversity of WashingtonSeattleUSA
  2. 2.Department of BiologyUniversity of UtahSalt Lake CityUSA
  3. 3.International Institute of Molecular and Cell BiologyWarsawPoland
  4. 4.Department of PharmacologyUniversity of WashingtonSeattleUSA
  5. 5.Department of ChemistryUniversity of WashingtonSeattleUSA
  6. 6.Department of OphthalmologyUniversity of UtahSalt Lake CityUSA
  7. 7.Department of Neurobiology and AnatomyUniversity of UtahSalt Lake CityUSA

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