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

    Fingerprint

    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, 06.2009, p. 2837-2846.

    Research output: Contribution to journalArticle

    Yeo, RL, Tsunekawa, K, Mi, JM, Haet, NU, Hwang, JI, 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 RL, Tsunekawa K, Mi JM, Haet NU, Hwang JI, Osugi T et al. Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates. Endocrinology. 2009 Jun;150(6):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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