Interactions of zebrafish peptide YYb with the neuropeptide Y-family receptors Y4, Y7, Y8a, and Y8b

Görel Sundström,Tomas A Larsson,Johan Heldin,Dan Larhammar,Bo Xu

doi:10.3389/fnins.2013.00029

Abstract

The neuropeptide Y (NPY) system influences numerous physiological functions including feeding behavior, endocrine regulation, and cardiovascular regulation. In jawed vertebrates it consists of 3–4 peptides and 4–7 receptors. Teleost fishes have unique duplicates of NPY and PYY as well as the Y8 receptor. In the zebrafish, the NPY system consists of the peptides NPYa, PYYa, and PYYb (NPYb appears to have been lost) and at least seven NPY receptors: Y1, Y2, Y2-2, Y4, Y7, Y8a, and Y8b. Previously PYYb binding has been reported for Y2 and Y2-2. To search for peptide-receptor preferences, we have investigated PYYb binding to four of the remaining receptors and compared with NPYa and PYYa. Taken together, the most striking observations are that PYYa displays reduced affinity for Y2 (3 nM) compared to the other peptides and receptors and that all three peptides have higher affinity for Y4 (0.028–0.034 nM) than for the other five receptors. The strongest peptide preference by any receptor selectivity is the one previously reported for PYYb by the Y2 receptor, as compared to NPY and PYYa. These affinity differences may be helpful to elucidate specific details of peptide-receptor interactions. Also, we have investigated the level of mRNA expression in different organs using qPCR. All peptides and receptors have higher expression in heart, kidney, and brain. These quantitative aspects on receptor affinities and mRNA distribution help provide a more complete picture of the NPY system.

Highlights

The neuropeptide Y (NPY) system of receptors and peptides in vertebrates is complex with 4–7 G-protein coupled receptors and 3–4 peptide ligands depending on the species
The receptor family expanded in the two whole genome duplications early in vertebrate evolution, resulting in a repertoire of seven receptors named Y1 through Y8 in a hypothetical ancestral gnathostome (Fredriksson et al, 2004). (Receptor Y3 is missing; this receptor was postulated from pharmacological studies but remains unidentified as a separate gene.) The full repertoire is still present in a cartilaginous fish, the elephant shark, Callorhinchus milii (Larsson et al, 2009)
We recently described a local duplicate of the Y2 receptor in zebrafish and medaka, called Y2-2 (Fallmar et al, 2011)

Summary

Introduction

The neuropeptide Y (NPY) system of receptors and peptides in vertebrates is complex with 4–7 G-protein coupled receptors and 3–4 peptide ligands depending on the species Members of both the receptor and peptide families have been found in invertebrates as well as vertebrates, suggesting an ancient origin of the system (Tensen et al, 1998; Garczynski et al, 2002; Hill et al, 2002; Larhammar and Salaneck, 2004). Medaka (Oryzias latipes) seems to have lost PYYb and zebrafish (Danio rerio) lacks NPYb (unless they have escaped sequencing in the genome projects), while other species with sequenced genomes have the full repertoire of four peptides: green spotted pufferfish (Tetraodon nigroviridis), fugu (Takifugu rubripes), and three-spined stickleback (Gasterosteus aculeatus) (Larsson et al, 2009)

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