상위피인용논문
- 조회1,936
Abstract
Yeo Reum Lee1,*, Kenta Tsunekawa1,*, 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, and Kazuyoshi Tsutsui
Laboratory of G Protein-Coupled Receptors (Y.R.L., M.J.M., H.N.U., J.-I.H., J.Y.S.), Graduate School of Medicine, Korea University, Seoul 136-705, Korea; Laboratory of Integrative Brain Sciences (K.Tsun., T.O., N.O., Y.S., K.Tsut.), Department of Biology, Waseda University, Tokyo 162-8480, Japan; School of Biological Sciences (K.K.), Seoul National University, Seoul 151-742, Korea; Institut National de la Sante´ et de la Recherche Me´ dicale Unite´ 413 (H.V.), Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (L’Institut Fe´d ´eratif de Recherches Multidisciplinaires sur les Peptides 23), University of Rouen, 76821 Mont-Saint-Aignan, France; and Hormone Research Center and School of Biological Sciences and Technology (H.B.K.), Chonnam National University, Gwangju 500-757, Korea
*Y.R.L. and K.Tsun. contributed equally to this work.
Address all correspondence and requests for reprints to: J. Y. Seong, Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea.K. Tsutsui, Department of Biology, Waseda University, Tokyo 162-8480, Japan.
Abstract
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.
Non-mammalian vertebrates possess two KiSS genes and two GPR54 genes (three KiSS genes and three GPR54 genes in the amphibian Xenopus tropicalis) that may serve distinct functions.
논문정보
- Research article
- 2009년 06월 (BRIC 등록일 2016-12-15)
- 국내(교신)+국외 연구진
- 120회 이상 인용된 논문
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