Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

GCAP (Guanylate Cyclase–Activating Protein)

  • Karl-Wilhelm KochEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_12


Historical Background

The primary processes of vertebrate visual excitation are located in the rod and cone photoreceptor cells of the retina. Illumination of the rod and cone cells triggers a biochemical cascade leading to hyperpolarization of the cell. This conversion of a light signal into an electrical signal is called phototransduction, and in the 1970s the concept of an intracellular second messenger mediating this process was developed. Two competing hypotheses were intensively discussed, the “calcium hypothesis” and the “cGMP hypothesis” to reconcile different lines of experimental results. With the identification of a cGMP-gated cation channel (cyclic nucleotide–gated channel, CNG-channel) in the plasma membrane of rod and cone cells, the second messenger of light excitation was finally identified (for a historical overview see Luo et al. 2008). Calcium on the other hand was found to be important for the sensitivity regulation...

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


  1. Behnen P, Dell’Orco D, Koch KW. Involvement of the calcium sensor GCAP1 in hereditary cone dystrophies. Biol Chem. 2010;391:631–7.PubMedCrossRefGoogle Scholar
  2. Burgoyne RD. Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signaling. Nat Rev Neurosci. 2007;8:182–93.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Dizhoor AM, Olshevskaya EV, Peshenko IV. Mg2+/Ca2+ cation binding cycle of guanylyl cylase activating proteins (GCAPs): role in regulation of photoreceptor guanylyl cyclase. Mol Cell Biochem. 2010;334:117–24.PubMedCrossRefGoogle Scholar
  4. Fain GL, Matthews HR, Cornwall C, Koutalos Y. Adaptation in vertebrate photoreceptors. Physiol Rev. 2001;81:117–51.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Imanishi Y, Yang L, Sokal I, Filipek S, Palczewski K, Baehr W. 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). J Mol Evol. 2004;59:204–17.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Koch KW, Dell’Orco D. A calcium relay mechanism in vertebrate phototransduction. ACS Chem Neurosci. 2013;4:909–17.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Koch KW, Stryer L. Highly cooperative feedback control of retinal rod guanylate cyclase by calcium ions. Nature. 1988;334:64–6.PubMedCrossRefGoogle Scholar
  8. Koch KW, Duda T, Sharma RK. Ca2+-modulated vision-linked ROS-GC guanylate cyclase transduction machinery. Mol Cell Biochem. 2010;334:105–15.PubMedCrossRefGoogle Scholar
  9. Luo DG, Xue T, Yau KW. How vision begins: an odyssey. Proc Natl Acad Sci USA. 2008;105:9855–62.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Rätscho N, Scholten A, Koch KW. Expression profiles of three novel sensory guanylate cyclases and guanylate cyclase-activating proteins in the zebrafish retina. Biochim Biophys Acta. 2009;1793:1110–4.PubMedCrossRefGoogle Scholar
  11. Rätscho N, Scholten A, Koch KW. Diversity of guanylate cyclases in teleost fishes. Mol Cell Biochem. 2010;334:207–14.PubMedCrossRefGoogle Scholar
  12. Stephen R, Bereta G, Golczak M, Palczewski K, Sousa MC. Stabilizing function for myristoyl group revealed by the crystal structure of a neuronal calcium sensor, guanylate cyclase-activating protein 1. Sturcture. 2007;15:1392–402.CrossRefGoogle Scholar
  13. Stephen R, Filipek S, Palczewski K, Sousa MC. Ca2+-dependent regulation of phototransduction. Photochem Photobiol. 2008;84:903–10.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Takemoto N, Tachibanaki S, Kawamura S. High cGMP synthetic activity in carp cones. Proc Natl Acad Sci USA. 2009;106:11788–93.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of NeurosciencesUniversity of OldenburgOldenburgGermany