Document Detail

Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates.
MedLine Citation:
PMID:  19164475     Owner:  NLM     Status:  MEDLINE    
Kisspeptin and its receptor GPR54 play important roles in mammalian reproduction and cancer metastasis. Because the KiSS and GPR54 genes have been identified in a limited number of vertebrate species, mainly in mammals, the evolutionary history of these genes is poorly understood. In the present study, we have cloned multiple forms of kisspeptin and GPR54 cDNAs from a variety of vertebrate species. We found that fish have two forms of kisspeptin genes, KiSS-1 and KiSS-2, whereas Xenopus possesses three forms of kisspeptin genes, KiSS-1a, KiSS-1b, and KiSS-2. The nonmammalian KiSS-1 gene was found to be the ortholog of the mammalian KiSS-1 gene, whereas the KiSS-2 gene is a novel form, encoding a C-terminally amidated dodecapeptide in the Xenopus brain. This study is the first to identify a mature form of KiSS-2 product in the brain of any vertebrate. Likewise, fish possess two receptors, GPR54-1 and GPR54-2, whereas Xenopus carry three receptors, GPR54-1a, GPR54-1b, and GPR54-2. Sequence identity and genome synteny analyses indicate that Xenopus GPR54-1a is a human GPR54 ortholog, whereas Xenopus GPR54-1b is a fish GPR54-1 ortholog. Both kisspeptins and GPR54s were abundantly expressed in the Xenopus brain, notably in the hypothalamus, suggesting that these ligand-receptor pairs have neuroendocrine and neuromodulatory roles. Synthetic KiSS-1 and KiSS-2 peptides activated GPR54s expressed in CV-1 cells with different potencies, indicating differential ligand selectivity. These data shed new light on the molecular evolution of the kisspeptin-GPR54 system in vertebrates.
Yeo Reum Lee; Kenta Tsunekawa; Mi Jin Moon; Haet Nim Um; Jong-Ik Hwang; Tomohiro Osugi; Naohito Otaki; Yuya Sunakawa; Kyungjin Kim; Hubert Vaudry; Hyuk Bang Kwon; Jae Young Seong; Kazuyoshi Tsutsui
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-22
Journal Detail:
Title:  Endocrinology     Volume:  150     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-21     Completed Date:  2009-06-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2837-46     Citation Subset:  AIM; IM    
Laboratory of G Protein-Coupled Receptors, Graduate School of Medicine, Korea University, Seoul, Korea.
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MeSH Terms
Amino Acid Sequence
DNA, Complementary / genetics
Evolution, Molecular*
Hypothalamus / metabolism
Molecular Sequence Data
Protein Isoforms / analysis,  genetics,  metabolism
RNA, Messenger / metabolism
Receptors, G-Protein-Coupled / analysis*,  genetics*,  metabolism
Tumor Suppressor Proteins / analysis*,  genetics*,  metabolism
Reg. No./Substance:
0/DNA, Complementary; 0/KISS1 protein, human; 0/KISS1R protein, human; 0/Kiss1r protein, mouse; 0/Protein Isoforms; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/Tumor Suppressor Proteins; 0/kisspeptin, mouse

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