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Discovery of a Novel Glucagon-like Peptide (GCGL) and Its Receptor (GCGLR) in Chickens: Evidence for the Existence of GCGL and GCGLR Genes in Nonmammalian Vertebrates

Discovery of a Novel Glucagon-like Peptide (GCGL) and Its Receptor (GCGLR) in Chickens: Evidence... AbstractGlucagon (GCG), glucagon-related peptides, and their receptors have been reported to play important roles including the regulation of glucose homeostasis, gastrointestinal activity, and food intake in vertebrates. In this study, we identified genes encoding a novel glucagon-like peptide (named GCGL) and its receptor (GCGLR) from adult chicken brain using RACE and/or RT-PCR. GCGL was predicted to encode a peptide of 29 amino acids (cGCGL1–29), which shares high amino acid sequence identity with mammalian and chicken GCG (62–66%). GCGLR is a receptor of 430 amino acids and shares relatively high amino acid sequence identity (53–55%) with the vertebrate GCG receptor (GCGR). Using a pGL3-CRE-luciferase reporter system, we demonstrated that synthetic cGCGL1–29, but not its structurally related peptides, i.e. exendin-4 and GCG, could potently activate GCGLR (EC50: 0.10 nm) expressed in Chinese hamster ovary cells, indicating that GCGLR can function as a GCGL-specific receptor. RT-PCR assay revealed that GCGL expression is mainly restricted to several tissues including various brain regions, spinal cord, and testes, whereas GCGLR mRNA is widely expressed in adult chicken tissues with abundant expression noted in the pituitary, spinal cord, and various brain regions. Using synteny analysis, GCGL and GCGLR genes were also identified in the genomes of fugu, tetraodon, tilapia, medaka, coelacanth, and Xenopus tropicalis. As a whole, the discovery of GCGL and GCGLR genes in chickens and other nonmammalian vertebrates clearly indicates a previously unidentified role of GCGL-GCGLR in nonmammalian vertebrates and provides important clues to the evolutionary history of GCG and GCGL genes in vertebrates. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Endocrinology Oxford University Press

Discovery of a Novel Glucagon-like Peptide (GCGL) and Its Receptor (GCGLR) in Chickens: Evidence for the Existence of GCGL and GCGLR Genes in Nonmammalian Vertebrates

Endocrinology , Volume 153 (11) – Nov 1, 2012

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References (65)

Publisher
Oxford University Press
Copyright
Copyright © 2012 by The Endocrine Society
ISSN
0013-7227
eISSN
1945-7170
DOI
10.1210/en.2012-1586
pmid
23015292
Publisher site
See Article on Publisher Site

Abstract

AbstractGlucagon (GCG), glucagon-related peptides, and their receptors have been reported to play important roles including the regulation of glucose homeostasis, gastrointestinal activity, and food intake in vertebrates. In this study, we identified genes encoding a novel glucagon-like peptide (named GCGL) and its receptor (GCGLR) from adult chicken brain using RACE and/or RT-PCR. GCGL was predicted to encode a peptide of 29 amino acids (cGCGL1–29), which shares high amino acid sequence identity with mammalian and chicken GCG (62–66%). GCGLR is a receptor of 430 amino acids and shares relatively high amino acid sequence identity (53–55%) with the vertebrate GCG receptor (GCGR). Using a pGL3-CRE-luciferase reporter system, we demonstrated that synthetic cGCGL1–29, but not its structurally related peptides, i.e. exendin-4 and GCG, could potently activate GCGLR (EC50: 0.10 nm) expressed in Chinese hamster ovary cells, indicating that GCGLR can function as a GCGL-specific receptor. RT-PCR assay revealed that GCGL expression is mainly restricted to several tissues including various brain regions, spinal cord, and testes, whereas GCGLR mRNA is widely expressed in adult chicken tissues with abundant expression noted in the pituitary, spinal cord, and various brain regions. Using synteny analysis, GCGL and GCGLR genes were also identified in the genomes of fugu, tetraodon, tilapia, medaka, coelacanth, and Xenopus tropicalis. As a whole, the discovery of GCGL and GCGLR genes in chickens and other nonmammalian vertebrates clearly indicates a previously unidentified role of GCGL-GCGLR in nonmammalian vertebrates and provides important clues to the evolutionary history of GCG and GCGL genes in vertebrates.

Journal

EndocrinologyOxford University Press

Published: Nov 1, 2012

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