Neuropeptide Y receptor subtype with unique properties cloned in the zebrafish: the zYa receptor

Starbäck, P., Lundell, I., Fredriksson, R., Berglund, M.M., Yan, Y.-L., Wraith, A., Söderberg, C., Postlethwait, J.H., and Larhammar, D.
Mol. Brain Res.   70(2): 242-252 (Journal)
Registered Authors
Larhammar, Dan, Postlethwait, John H., Yan, Yi-Lin
neuropeptide Y; peptide YY; G-protein-coupled receptor; microphysiometer; zebrafish; evolution; gene family; chromosomal mapping
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • COS Cells
  • Chromosome Mapping*
  • Cloning, Molecular
  • Conserved Sequence
  • Cricetinae
  • Humans
  • Kinetics
  • Mammals
  • Mice
  • Molecular Sequence Data
  • Neuropeptide Y/metabolism
  • Peptide YY/metabolism
  • Phylogeny
  • Rats
  • Receptors, Neuropeptide Y/chemistry
  • Receptors, Neuropeptide Y/genetics*
  • Receptors, Neuropeptide Y/metabolism*
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection
  • Xenopus laevis
  • Zebrafish
10407172 Full text @ Mol. Brain Res.
Neuropeptide Y (NPY) belongs to a family of structurally related neuroendocrine peptides for which five different G-protein-coupled receptor subtypes have been cloned in mammals. To identify additional subtypes we have performed PCR with degenerate primers in different species. We describe here the cloning and pharmacological profile of a unique NPY receptor subtype in the zebrafish that has tentatively been called the zYa receptor. It has 46-50% amino acid identity to the mammalian Y1, Y4 and y6 receptors and the previously cloned zebrafish receptors zYb and zYc, and only about 27% to Y2 and Y5. The zYa receptor binds NPY and PYY from mammals as well as zebrafish with high affinities and has a K(d) of 28 pM for porcine (125)I-PYY. It has a unique binding profile displaying some features in common with each of the mammalian Y1, Y2 and Y5 receptors. In a microphysiometer assay the receptor responds with extracellular acidification. Chromosomal mapping in the zebrafish genome of zYa, zYb and zYc receptor genes indicates a possible orthologous relationship between zYc and mammalian y6, but identifies no obvious mammalian ortholog for zYa (zYb is a recent copy of zYc in the fish lineage). These results imply that previous studies of NPY in fishes, which have strived to interpret the effects within the framework of mammalian Y1, Y2, and Y5 receptors, need to be reevaluated. Thus, the sequence comparisons, pharmacological properties, and chromosomal localization suggest that the zYa receptor is a novel NPY receptor subtype which is likely to be present also in mammals.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes