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)

Imanishi, Y., Yang, L., Sokal, I., Filipek, S., Palczewski, K., and Baehr, W.
Journal of molecular evolution   59(2): 204-217 (Journal)
Registered Authors
Guanylate cyclase; Guanylate cyclase-activating proteins; Phototransduction; Ca2+-binding proteins; Rod and cone photoreceptors
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Composition
  • Base Sequence
  • Calcium-Binding Proteins/genetics*
  • Calcium-Binding Proteins/metabolism
  • Cloning, Molecular
  • Cluster Analysis
  • DNA Primers
  • Databases, Genetic
  • Gene Expression*
  • Genetic Variation*
  • Guanylate Cyclase-Activating Proteins
  • In Situ Hybridization
  • Models, Genetic
  • Molecular Sequence Data
  • Phylogeny*
  • Protein Conformation
  • Retina/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Takifugu/genetics*
  • Zebrafish/genetics*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
15486694 Full text @ J. Mol. Evol.
The guanylate cyclase-activating proteins (GCAPs) are Ca 2+-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 fuGCAP1-8, fuGCIP, zGCAP1-5, zGCAPV 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 zGCAP1 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.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes