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 for the existence of GCGL and GCGLR genes in nonmammalian vertebrates.
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DOI：
10.1210/en.2012-1586
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发表时间：
2012-09
期刊：
影响因子：
4.8
通讯作者：
Yajun Wang;F. Meng;Y. Zhong;Guian Huang;Juan Li
中科院分区：
文献类型：
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作者：
Yajun Wang;F. Meng;Y. Zhong;Guian Huang;Juan Li
胰升糖素(GCG)、胰升糖素相关多肽及其受体在调节脊椎动物的葡萄糖稳态、胃肠活动和摄食等方面发挥着重要作用。在本研究中，我们利用RACE和/或RT-PCR从成年鸡脑中克隆了一种新的胰升糖素样肽(命名为GCGL)及其受体(GCGLR)的编码基因。GCGL编码29个氨基酸(cGCGL(1-29))，与哺乳动物和鸡GCG有较高的氨基酸序列同源性(62-66%)。GCGLR是一个由430个氨基酸组成的受体，与脊椎动物的GCG受体(GCGR)有较高的氨基酸序列同源性(53-55%)。利用pGL3-Cre-荧光素酶报告系统，我们证明了合成的cGCGL(1-29)能够有效地激活中国仓鼠卵巢细胞表达的GCGLR(EC(50)：0.10 nm)，这表明GCGLR可以作为GCGL特异性受体发挥作用。RT-PCR分析表明，GCGL主要在不同脑区、脊髓和睾丸等组织中表达，而GCGLR在成年鸡组织中广泛表达，在脑垂体、脊髓和不同脑区表达丰富。通过共时分析，GCGL和GCGLR基因也在河豚、四齿鲨、罗非鱼、青蛙、腔棘鱼和热带非洲爪哇的基因组中得到了鉴定。总体而言，在鸡和其他非哺乳动物脊椎动物中发现的GCGL和GCGLR基因清楚地表明了GCGL-GCGLR在非哺乳动物脊椎动物中的作用，并为脊椎动物GCG和GCGL基因的进化史提供了重要线索。
Glucagon (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 (cGCGL(1-29)), 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 cGCGL(1-29), but not its structurally related peptides, i.e. exendin-4 and GCG, could potently activate GCGLR (EC(50): 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.