Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates

Reum Lee Yeo, Kenta Tsunekawa, Jin Moon Mi, Nim Um Haet, Jong-Ik Hwang, Tomohiro Osugi, Naohito Otaki, Yuya Sunakawa, Kyungjin Kim, Hubert Vaudry, Bang Kwon Hyuk, Jae Young Seong, Kazuyoshi Tsutsui

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2837-2846
Number of pages10
JournalEndocrinology
Volume150
Issue number6
DOIs
Publication statusPublished - 2009 Jun 1

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Kisspeptins
Molecular Evolution
Xenopus
Vertebrates
Genes
Fishes
Brain
Ligands
Synteny
Hypothalamus
Reproduction
Mammals
Complementary DNA
History
Genome
Neoplasm Metastasis
Peptides

ASJC Scopus subject areas

  • Endocrinology

Cite this

Yeo, R. L., Tsunekawa, K., Mi, J. M., Haet, N. U., Hwang, J-I., Osugi, T., ... Tsutsui, K. (2009). Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology, 150(6), 2837-2846. https://doi.org/10.1210/en.2008-1679

Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. / Yeo, Reum Lee; Tsunekawa, Kenta; Mi, Jin Moon; Haet, Nim Um; Hwang, Jong-Ik; Osugi, Tomohiro; Otaki, Naohito; Sunakawa, Yuya; Kim, Kyungjin; Vaudry, Hubert; Hyuk, Bang Kwon; Seong, Jae Young; Tsutsui, Kazuyoshi.

In: Endocrinology, Vol. 150, No. 6, 01.06.2009, p. 2837-2846.

Research output: Contribution to journalArticle

Yeo, RL, Tsunekawa, K, Mi, JM, Haet, NU, Hwang, J-I, Osugi, T, Otaki, N, Sunakawa, Y, Kim, K, Vaudry, H, Hyuk, BK, Seong, JY & Tsutsui, K 2009, 'Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates', Endocrinology, vol. 150, no. 6, pp. 2837-2846. https://doi.org/10.1210/en.2008-1679
Yeo, Reum Lee ; Tsunekawa, Kenta ; Mi, Jin Moon ; Haet, Nim Um ; Hwang, Jong-Ik ; Osugi, Tomohiro ; Otaki, Naohito ; Sunakawa, Yuya ; Kim, Kyungjin ; Vaudry, Hubert ; Hyuk, Bang Kwon ; Seong, Jae Young ; Tsutsui, Kazuyoshi. / Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. In: Endocrinology. 2009 ; Vol. 150, No. 6. pp. 2837-2846.
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