This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Google Scholar Articles by Lee, Y. R. Articles by Tsutsui, K. PubMed PubMed Citation Articles by Lee, Y. R. Articles by Tsutsui, K.

Molecular Evolution of Multiple Forms of Kisspeptins and GPR54 Receptors in Vertebrates

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 Santé et de la Recherche Médicale Unité 413 (H.V.), Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (L’Institut Fédératif 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

Address all correspondence and requests for reprints to: J. Y. Seong, Graduate School of Medicine, Korea University, Seoul 136-705, Republic of Korea. E-mail: jyseong{at}korea.ac.kr; or K. Tsutsui, Department of Biology, Waseda University, Tokyo 162-8480, Japan. E-mail: k-tsutsui{at}waseda.jp.

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.

This article has been cited by other articles:

				A. E. Oakley, D. K. Clifton, and R. A. Steiner Kisspeptin Signaling in the Brain Endocr. Rev., October 1, 2009; 30(6): 713 - 743. [Abstract] [Full Text] [PDF]