Skip to main content
SpringerLink
Log in

GCAPs: Ca2+-Sensitive Regulators of retGC

  • Chapter
Photoreceptors and Calcium

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 514))

Abstract

Lowered concentration of Ca2+ions, resulting from illumination of the photoreceptor cell, is the signal for resynthesis of cGMP by retina-specific guanylyl cyclase (retGC). This Ca2+-dependent activation of retGC is mediated by Ca2+-binding proteins named GCAPs (guanylyl cyclase-activating proteins) and contributes to the recovery of photoreceptor cell to the dark state. Three different GCAPs (GCAP1, GCAP2 and GCAP3) are identified in vertebrate retina to date. In this chapter we describe their discovery, methods of purification, properties, and possible modes of action.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Palczewski K, Polans AS, Baehr W et al. Ca2+-binding proteins in the retina: structure, function, and the etiology of human visual diseases. BioEssays 2000; 22:337–350.

    Article  PubMed  CAS  Google Scholar 

  2. Gorczyca WA. Role of calcium ions in vertebrate phototransduction. Pol J Pharmacol 1999; 51:167–72

    PubMed  CAS  Google Scholar 

  3. Dizhoor AM. Regulation of cGMP synthesis in photoreceptors: role in signal transduction and congenital diseases of the retina. Cell Signal 2000; 12: 711–719.

    Article  PubMed  CAS  Google Scholar 

  4. Kobialka M, Gorczyca WA. Particulate guanylyl cyclases: multiple mechanisms of activation. Acta Biochim Pol 2000; 47:517–528.

    PubMed  CAS  Google Scholar 

  5. Lucas KA, Pitari GM, Kazerounian S et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 2000; 52:375–413.

    PubMed  CAS  Google Scholar 

  6. Lolley RN, Racz E Calcium modulation of cyclic GMP synthesis in rat visual cells. Vision Res 1982; 22:1481–1486.

    Article  PubMed  CAS  Google Scholar 

  7. Koch K.-W, Stryer L Highly cooperative feedback control of retinal rod guanylate cyclase by calcium ions. Nature 1988; 334:64–66.

    Article  PubMed  CAS  Google Scholar 

  8. Shyjan AW, de Sauvage FJ, Gillett NA, et al. Molecular cloning of a retina-specific membrane guanylyl cyclase. Neuron 1992; 9:727–737

    Article  PubMed  CAS  Google Scholar 

  9. Gorczyca WA, Gray-Keller MP, Detwiler PB, et al. Purification and physiological evaluation of a guanylate cyclase activating protein from retinal rods. Proc Natl Acad Sci USA 1994; 91:4014–8.

    Article  PubMed  CAS  Google Scholar 

  10. Palczewski K, Subbaraya I, Gorczyca WA et al. Molecular cloning and characterization of retinal photoreceptor guanylyl cyclase-activating protein. Neuron 1994; 13:395–404.

    Article  PubMed  CAS  Google Scholar 

  11. Dizhoor AM, Lowe DG, Olshevskaya EV et al. The human photoreceptor membrane guanylyl cyclase, RetGC, is present in outer segments and is regulated by calcium and a soluble activator. Neuron 1994; 12:1345–52.

    Article  PubMed  CAS  Google Scholar 

  12. Gorczyca WA, Polans AS, Surgucheva IG et al. Guanylyl cyclase activating protein. A calcium-sensitive regulator of phototransduction. J Biol Chem 1995; 270:22029–36.

    Article  PubMed  CAS  Google Scholar 

  13. Dizhoor AM, Olshevskaya EV, Henzel WJ et al. Cloning, sequencing, and expression of a 24-kDa Ca(2+)-binding protein activating photoreceptor guanylyl cyclase. J Biol Chem 1995; 270:25200–6.

    Article  PubMed  CAS  Google Scholar 

  14. Goraczniak RM, Duda T, Sitaramayya A et al. Structural and functional characterization of the rod outer segment membrane guanylate cyclase. Biochem J 1994; 302:455–461.

    PubMed  CAS  Google Scholar 

  15. Lowe DG, Dizhoor AM, Liu K et al. Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2. Proc Natl Acad Sci U S A 1995; 92:5535–9

    Article  PubMed  CAS  Google Scholar 

  16. Yang R-B, Foster DC, Garbers DL et al. Two membrane forms of guanylyl cyclase found in the eye. Proc natl Acad Sci USA 1995; 92:602–606.

    Article  PubMed  CAS  Google Scholar 

  17. Goraczniak RM, Duda T, Sharma RK Structural and functional characterization of a second subfamily member of the calcium-modulated bovine rod outer segment membrane guanylate cyclase, ROS-GC2. Biochem Biophys Res Commun 1997; 234:666–670.

    Article  CAS  Google Scholar 

  18. Haeseleer F, Sokal I, Li N et al. Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily. J Biol Chem 1999; 274:6526–35.

    Article  PubMed  CAS  Google Scholar 

  19. Imanishi Y, Li N, Sokal I, et al. Characterization of retinal guanylyl-cyclase activating protein 3(GCAP3) from zebrafish to man. Eur J Neurosci 2002; 15:63–78.

    Article  PubMed  Google Scholar 

  20. Frins S, Bönigk W, Müller F et al. Functional characterization of a guanylyl cyclase-activating protein from vertebrate rods. Cloning, heterologous expression, and localization. J Biol Chem 1996; 271:8022–7.

    Article  PubMed  CAS  Google Scholar 

  21. Polans A, Baehr W, Palczewski K. Turned on by Ca2+! The physiology and pathology of Ca(2+)-binding proteins in the retina. Trends Neurosci 1996; 19:547–54.

    Article  PubMed  CAS  Google Scholar 

  22. Burgoyne RD, Weiss JL. The neuronal calcium sensor family of Ca2+-binding proteins. Biochem J 2001; 353:1–12.

    Article  PubMed  CAS  Google Scholar 

  23. Subbaraya I, Ruiz CC, Helekar BS et al. Molecular characterization of human and mouse photoreceptor guanylate cyclase-activating protein (GCAP) and chromosomal localization of the human gene. J Biol Chem 1994; 269:31080–9.

    PubMed  CAS  Google Scholar 

  24. Surguchov A, Bronson JD, Banerjee P et al. The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on the short arm of chromosome 6 (p21.I). Genomics 1997; 39:312–22.

    Article  PubMed  CAS  Google Scholar 

  25. Olshevskaya EV, Hughes RE, Hurley JB et al. Calcium binding, but not a calcium-myristoyl switch, controls the ability of guanylyl cyclase-activating protein GCAP-2 to regulate photoreceptor guanylyl cyclase. J Biol Chem 1997; 272:14327–33.

    Article  PubMed  CAS  Google Scholar 

  26. Otto-Bruc A, Fariss RN, Haeseleer F, et al. Localization of guanylate cyclase-activating protein 2 in mammalian retinas. Proc Natl Acad Sci USA 1997; 94:4727–32.

    Article  PubMed  CAS  Google Scholar 

  27. Ames JB, Dizhoor AM, Ikura M et al. Three-dimensional structure of guanylyl cyclase activating protein-2, a calcium-sensitive modulator of photoreceptor guanylyl cyclases. J Biol Chem 1999; 274:19329–37.

    Article  PubMed  CAS  Google Scholar 

  28. Otto-Bruc A, Buczylko J, Surgucheva I et al. Functional reconstitution of photoreceptor guanylate cyclase with native and mutant forms of guanylate cyclase-activating protein 1. Biochemistry 1997; 36:4295–302.

    Article  PubMed  CAS  Google Scholar 

  29. Sokal I, Otto-Bruc AE, Surgucheva I et al. Conformational changes in guanylyl cyclase-activating protein 1 (GCAP1) and its tryptophan mutants as a function of calcium concentration. J Biol Chem 1999; 274:19829–37.

    Article  PubMed  CAS  Google Scholar 

  30. Sokal I, Li N, Klug CS et al. Calcium-sensitive regions of GCAP1 as observed by chemical modifications, flourescence and EPR spectroscopies. J Biol Chem 2001; 46:43361–43373.

    Article  Google Scholar 

  31. Hughes RE, Brzovic PS, Dizhoor AM et al. Ca2+-dependent conformational changes in bovine GCAP-2. Protein Sci 1998; 7:2675–80.

    Article  PubMed  CAS  Google Scholar 

  32. Dizhoor AM, Hurley JB. Inactivation of EF-hands makes GCAP-2 (p24) a constitutive activator of photoreceptor guanylyl cyclase by preventing a Ca2tinduced, “activator-to-inhibitor” transition. J Biol Chem 1996; 271:19346–50

    Article  PubMed  CAS  Google Scholar 

  33. Rudnicka-Nawrot M, Surgucheva I, Hulmes JD et al. Changes in biological activity and folding of guanylate cyclase-activating protein 1 as a function of calcium. Biochemistry 1998; 37:248–57.

    Article  PubMed  CAS  Google Scholar 

  34. Sokal I, Li N, Surgucheva I, Warren MJ et al. GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy. Mol Cell 1998; 2:129–33.

    Article  PubMed  CAS  Google Scholar 

  35. Dizhoor AM, Boikov SG, Olshevskaya EV. Constitutive activation of photoreceptor guanylate cyclase by Y99C mutant of GCAP-1. Possible role in causing human autosomal dominant cone degeneration. J Biol Chem 1998; 273:17311–4.

    Article  PubMed  CAS  Google Scholar 

  36. Gorczyca WA, Van Hooser JP, Palczewski K. Nucleotide inhibitors and activators of retinal guanylyl cyclase. Biochemistry 1994; 33:3217–22.

    Article  PubMed  CAS  Google Scholar 

  37. Gorczyca WA. Use of nucleoside alpha-phosphorothioates in studies of photoreceptor guanylyl cyclase: purification of guanylyl cyclase activating proteins. Methods Enzymol 2000; 315:689–707.

    Article  PubMed  CAS  Google Scholar 

  38. Cuenca N, Lopez S, Howes K, et al. The localization of guanylyl cyclase-activating proteins in the mammalian retina. Invest Ophthalmol Vis Sci 1998; 39:1243–50.

    PubMed  CAS  Google Scholar 

  39. Kachi S, Nishizawa Y, Olshevskaya E, et al. Detailed localization of photoreceptor guanylate cyclase activating protein-1 and -2 in mammalian retinas using light and electron microscopy. Exp Eye Res 1999; 68:465–73.

    Article  PubMed  CAS  Google Scholar 

  40. Venkataraman V, Nagele R, Duda T, et al. Rod outer segment membrane guanylate cyclase type I-linked stimulatory and inhibitory calcium signaling systems in the pineal gland: biochemical, molecular, and immunohistochemical evidence. Biochemistry 2000; 39:6042–52.

    Article  PubMed  CAS  Google Scholar 

  41. Semple-Rowland SL, Larkin P, Bronson JD, et al. Characterization of the chicken GCAP gene array and analyses of GCAP1, GCAP2, and GC1 gene expression in normal and rd chicken pineal. Mol Vis 1999; 5:14.

    PubMed  CAS  Google Scholar 

  42. Duda T, Goraczniak R, Surgucheva I, et al. Calcium modulation of bovine photoreceptor guanylate cyclase. Biochemistry 1996; 35:8478–82.

    Article  PubMed  CAS  Google Scholar 

  43. Laura RP, Dizhoor AM, Hurley JB. The membrane guanylyl cyclase, retinal guanylyl cyclase-1, is activated through its intracellular domain. J Biol Chem 1996; 271:11646–51.

    Article  PubMed  CAS  Google Scholar 

  44. Tucker CL, Laura RP, Hurley JB. Domain-specific stabilization of photoreceptor membrane guanylyl cyclase by adenine nucleotides and guanylyl cyclase activating proteins (GCAPs). Biochemistry 1997; 36:11995–2000.

    Article  PubMed  CAS  Google Scholar 

  45. Laura RP, Hurley JB. The kinase homology domain of retinal guanylyl cyclases I and 2 specifies the affinity and cooperativity of interaction with guanylyl cyclase activating protein-2. Biochemistry 1998; 37:11264–71.

    Article  PubMed  CAS  Google Scholar 

  46. Sokal I, Haeseleer F, Arendt A, et al. Identification of a guanylyl cyclase-activating protein-binding site within the catalytic domain of retinal guanylyl cyclase 1. Biochemistry 1999; 38:1387–93.

    Article  PubMed  CAS  Google Scholar 

  47. Olshevskaya EV, Boikov S, Ermilov A, et al. Mapping functional domains of the guanylatecyclaseregulator protein, GCAP-2. J Biol Chem 1999; 274:10823–32.

    Article  PubMed  CAS  Google Scholar 

  48. Schrem A, Lange C, Beyermann M, et al. Identification of a domain in guanylyl cyclase-activating protein 1 that interacts with a complex of guanylyl cyclase and tubulin in photoreceptors. J Biol Chem 1999: 274:6244–9.

    Article  PubMed  CAS  Google Scholar 

  49. Krylov DM, Niemi GA, Dizhoor AM, et al. Mapping sites in guanylyl cyclase activating protein-1 required for regulation of photoreceptor membrane guanylyl cyclases. J Biol Chem 1999; 274:10833–9.

    Article  PubMed  CAS  Google Scholar 

  50. Ermilov A.N., Olshevskaya E.V., Dizhoor A.M. Instead of binding calcium, one of the EF-hand structures in guanylyl cyclase activating protein-2 is required for targeting photoreceptor guanylyl cyclase. J Biol Chem 2001; 276:48143–48.

    PubMed  CAS  Google Scholar 

  51. Li N, Sokal I, Bronson JD, et al. Identification of functional regions of guanylate cyclase-activating protein 1 (GCAPI) using GCAPI/GCIP chimeras. Biol Chem 2001; 382:1179–1188.

    PubMed  CAS  Google Scholar 

  52. Sokal I, Alekseev A, Baehr W, et al. Soluble fusion proteins between single transmembrane photoreceptor guanylyl cyclases and their activators. Biochemistry 2002; 41:251–257.

    Article  PubMed  CAS  Google Scholar 

  53. Yu H, Olshevskaya E, Duda T, et al. Activation of retinal guanylyl cyclase-I by Ca2+-binding proteins involves its dimerization. J Biol Chem 1999; 274:15547–55.

    Article  PubMed  CAS  Google Scholar 

  54. Olshevskaya EV, Ermilov AN, Dizhoor AM. Dimerization of guanylyl cyclase-activating protein and a mechanism of photoreceptor guanylyl cyclase activation. J Biol Chem 1999; 274:25583–7

    Article  PubMed  CAS  Google Scholar 

  55. Tesmer JJ, Sunahara RK, Gilman AG, et al. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsa:GTPgS. Science 1997; 278: 1907–1916.

    Article  PubMed  CAS  Google Scholar 

  56. Payne AM, Downes SM, Bessant DA, et al. A mutation in guanylate cyclase activator IA (GUCAIA) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. Hum Mol Genet 1998; 7:273–277.

    Article  PubMed  CAS  Google Scholar 

  57. Mendez A, Burns ME, Sokal I, et al. Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proc Natl Acad Sci USA 2001; 98:9948–9953.

    Article  PubMed  CAS  Google Scholar 

  58. Howes KA, Pennesi ME, Sokal I, et al. GCAPI rescues rod photoreceptor response in GCAPI/ GCAP2 knockout mice. EMBO J, 2002; 21:1545–54.

    Article  PubMed  CAS  Google Scholar 

  59. Howes K, Bronson JD, Dang YL, et al. Gene array and expression of mouse retina guanylate cyclase activating proteins 1 and 2. Invest Ophthalmol Vis Sci 1998; 39:867–75.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Laboratory of Signaling Proteins, Poland

    Wojciech A. Gorczyca

  2. Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland

    Wojciech A. Gorczyca

  3. Department of Ophthalmology, School of Medicine, University of Washington, Seattle, Washington, USA

    Izabela Sokal

Authors
  1. Wojciech A. Gorczyca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Izabela Sokal
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Moran Eye Center/EIHG, University of Utah Health Science Center, 15 North/ 2030 East, Salt Lake City, UT, 84112-5330, USA

    Wolfgang Baehr Ph.D.

  2. Department of Ophthalmology, University of Washington, 1959 NE Pacific St., Seattle, WA, 98195, USA

    Krzysztof Palczewski Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gorczyca, W.A., Sokal, I. (2002). GCAPs: Ca2+-Sensitive Regulators of retGC. In: Baehr, W., Palczewski, K. (eds) Photoreceptors and Calcium. Advances in Experimental Medicine and Biology, vol 514. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0121-3_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0121-3_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4933-4

  • Online ISBN: 978-1-4615-0121-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation