The secretin G-protein-coupled receptor family: teleost receptors

Abstract

Twenty-one members of the secretin family (family 2) of G-protein-coupled receptors (GPCRs) were identified via directed cloning and data-mining of the Fugu Genome Consortium database, representing the most comprehensive description of secretin GPCRs in a teleost fish to date. Duplicated genes were identified for many of the family members, namely the receptors for pituitary adenylate cyclase-activating polypeptide (PACAP)/vasoactive intestinal peptide (VIP), calcitonin, calcitonin gene-related peptide (CGRP), growth hormone releasing hormone (GHRH), glucagon receptor/glucagon-like peptide (GLP) and parathyroid hormone-related peptide (PTHrP)/PTH. Mining of other teleost genomes (zebrafish and Tetraodon) revealed that the duplicated genes identified in the Takifugu genome were also present in these fish. Additional database searching of the Escherichia coli, yeast, Drosophila, Caenorhabditis elegans and Ciona genomes revealed that the family 2 of GPCRs were only present in the multicellular organisms. Orthologues of all the human secretin receptors were identified with the exception of secretin itself. Additional database searches in the Fugu Genome Consortium database also failed to reveal a secretin ligand and so it is hypothesised that both the receptor and the ligand evolved after the divergence of teleost/tetrapod lineages. Phylogenetic analysis at both the protein and the DNA level provided strong support for each of the individual receptor family groupings, but weak support between groups, making evolutionary inferences difficult. A more critical analysis of the PACAP/VIP receptor family confirmed previous hypotheses that the vasoactive intestinal peptide receptor (VPAC 1 R) gene is the ancestral form of the receptor.

Evidence of a reproduction-related function for pituitary adenylate cyclase-activating polypeptide-related peptide in an Anabantidae fish

“…Similar to bgPRP in in vitro assays, a sex-dependent effect of fGHRH on bFSH and GH gene expression was demonstrated in this study, probably because the receptors are structurally related (Cardoso et al 2005). Functional assays revealed that the PRP receptors in both zebrafish and goldfish are most sensitive to one of their PRP, but both also bind GHRH ).…”

Newly-identified receptors for peptide histidine-isoleucine and GHRH-like peptide in zebrafish help to elucidate the mammalian secretin superfamily

“…Third, in NJ and ML phylogenetic trees, fugu VPAC2RA and VPAC2RB cluster more closely with zebrafish PHIR than with chicken and human VPAC2R. However, the sequence similarity may not represent functional equivalence as addressed by Cardoso et al (2005). Whether fugu VPAC2RA and VPAC2RB are PHI receptors will be defined by functional assays.…”

“…The remaining three genes each encode only a single hormone: growth hormone-releasing hormone (GHRH), secretin (SCT), or glucose-dependent insulinotropic polypeptide (GIP). The nine receptors that bind these hormones are also structurally related as seven transmembrane receptors, which are grouped within the type B (or type 2) family of G-proteincoupled receptors , Ulloa-Aguirre & Conn 2000, Cardoso et al 2005 and named by the International Union of Pharmacology (Foord et al 2005). An understanding of the evolutionary history of the secretin superfamily of hormones and receptors may help to explain the gene organization, receptor binding, and function of this group of hormones.…”

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…In frog, however, VPAC1-R is able to bind both VIP and PACAP (Alexandre et al, 2000a), suggesting that the receptor ability to interact with PACAP could have emerged only after the divergence giving rise to the tetrapod lineage. In fact, based on gene prediction of the class II B receptor family in teleosts, it has been proposed that the VPAC1-R gene is the ancestral form of the receptor (Cardoso et al, 2005). Thus, the first VIP/PACAP receptor possibly interacted specifically with VIP but not with PACAP.…”