TAILIEUCHUNG - Báo cáo Y học: A neuropeptide Y receptor Y1-subfamily gene from an agnathan, the European river lamprey

A potential ancestral gene Erik Salaneck1, Robert Fredriksson1, Earl T. Larson1, J. Michael Conlon2 and Dan Larhammar1 Unit of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden; 2Regulatory Peptide Center, Creighton University School of Medicine, Omaha, Nebraska, USA We report here the isolation and functional expression of a neuropeptide Y (NPY) receptor from the river lamprey, Lampetra fluviatilis. The receptor displays | Eur. J. Biochem. 268 6146-6154 2001 FEBS 2001 A neuropeptide Y receptor Yl-subfamily gene from an agnathan the European river lamprey A potential ancestral gene Erik Salaneck1 Robert Fredriksson1 Earl T. Larson1 J. Michael Conlon2 and Dan Larhammar1 1Unit of Pharmacology Department of Neuroscience Uppsala University Uppsala Sweden 2Regulatory Peptide Center Creighton University School of Medicine Omaha Nebraska USA We report here the isolation and functional expression of a neuropeptide Y NPY receptor from the river lamprey Lampetra fluviatilis. The receptor displays 50 aminoacid sequence identity to all previously cloned Y1-sub-family receptors including Y1 Y4 and y6 and the teleost subtypes Ya Yb and Yc. Phylogenetic analyses point to a closer relationship with Y4 and Ya b c suggesting that the lamprey receptor could possibly represent a pro-orthologue of some or all of those gnathostome receptors. Our results support the notion that the Y1 subfamily increased in number by genome or large-scale chromosome duplications one of which may have taken place prior to the divergence of lampreys and gnathostomes whereas the second duplication probably occurred in the gnathostome lineage after this split. Functional expression of the lamprey receptor in a cell line facilitated specific binding of the three endogenous lamprey peptides NPY peptide YY and peptide MY with picomolar affinities. Binding studies with a large panel of NPY analogues revealed indiscriminate binding properties similar to those of another nonselective Y1-subfamily receptor zebrafish Ya. RT-PCR detected receptor mRNA in the central nervous system as well as in several peripheral organs suggesting diverse functions. This lamprey receptor is evolutionarily the most distant NPY receptor that clearly belongs to the Y1 subfamily as defined in mammals which shows that subtypes Y2 and Y5 arose even earlier in evolution. Keywords NPY PYY evolution gene duplication G-protein coupled receptor Lamprey. .

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