The localization of guanylyl cyclase-activating proteins in the mammalian retina

Invest Ophthalmol Vis Sci. 1998 Jun;39(7):1243-50.


Purpose: To explore the distribution of guanylyl cylase-activating proteins 1 and 2 (GCAP1 and GCAP2) in the mammalian retina.

Methods: Cryostat and vibratome vertical sections and wholemount retinas from mouse, rat, cat, bovine, monkey, and human eyes were prepared for immunocytochemistry and viewing by light and confocal microscopy.

Results: In all mammalian retinas investigated, intense GCAP1 immunoreactivity (GCAP1-IR) was seen in cone photoreceptor inner and outer segments, cell bodies, and synaptic regions. Intensity of the GCAP1-IR was strong in inner segments of rods in all species but weaker in outer segments-particularly so in primates and cats. GCAP2 immunoreactivity (GCAP2-IR) was weak in bovine, mouse, and rat cones but was intense in human and monkey cones. In all species except primates, GCAP2 staining was intense in rod inner and outer segments. In primates GCAP2-IR was intense in the rod inner segment but faint in the rod outer segment. A striking difference from the GCAP1 pattern of immunoreactivity was seen with GCAP2 antibodies as far as the inner retina was concerned. GCAP2-IR was evident in certain populations of bipolar, amacrine, and ganglion cells in all species.

Conclusions: GCAP1 and GCAP2, which are involved in Ca2+-dependent stimulation and inhibition of photoreceptor guanylyl cyclase, can be detected in mammalian photoreceptor inner and outer segments, consistent with their physiological function. The occurrence of both GCAPs in the synaptic region of the photoreceptors indicates participation of these proteins in pathways other than regulation of phototransduction. The occurrence of GCAP2 in inner retinal neurons is indicative of second-messenger chemical transduction, possibly in metabotropic glutamate, gamma-aminobutyric acid (GABA) receptor, and nitric oxide-activated neural circuits.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cats
  • Cattle
  • Fluorescent Antibody Technique, Indirect
  • Guanylate Cyclase / metabolism*
  • Guanylate Cyclase-Activating Proteins
  • Humans
  • Immunoenzyme Techniques
  • Macaca
  • Mice
  • Microscopy, Confocal
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Photoreceptor Cells / metabolism
  • Rats
  • Retina / metabolism*
  • Retinal Ganglion Cells / metabolism


  • Calcium-Binding Proteins
  • GUCA1A protein, human
  • GUCA1B protein, human
  • Guanylate Cyclase-Activating Proteins
  • Guca1a protein, mouse
  • Guca1b protein, mouse
  • Nerve Tissue Proteins
  • Guanylate Cyclase