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Um, Haet Nim,Han, Ji Man,Hwang, Jong-Ik,Hong, Sung In,Vaudry, Hubert,Seong, Jae Young Wiley (Blackwell Publishing) 2010 Annals of the New York Academy of Sciences Vol.1200 No.1
<P>Kisspeptin and its receptor, GPR54, play a pivotal role in vertebrate reproduction. Recent advances in bioinformatic tools combined with comparative genomics have led to the identification of a large number of kisspeptin and GPR54 genes in a variety of vertebrate species. Genome duplications may have produced at least two isoforms of both ligand (KiSS1 and KiSS2) and receptor (GPR54-1 and GPR54-2). Additional isoforms of kisspeptin (KiSS1b) and GPR54 (GPR54-1b) have been found in an amphibian species, Xenopus (Silurana) tropicalis. Here, we describe the evolutionary lineages of these kisspeptin and GPR54 isoforms using genome synteny and phylogenetic analyses, and possible molecular interactions between kisspeptin and GPR54 subtypes based on ligand-receptor selectivity. Together, kisspeptin and GPR54 provide an excellent model for understanding molecular coevolution of the peptide ligand and GPCR pairs.</P>
Hwang, Jong-Ik,Kim, Dong-Kyu,Kwon, Hyuk Bang,Vaudry, Hubert,Seong, Jae Young Wiley (Blackwell Publishing) 2009 Annals of the New York Academy of Sciences Vol.1163 No.1
<P>Neurotensin (NTS) plays important roles in neurotransmission and neuromodulation in the nervous system. NTS exerts its effects mainly by binding to the neurotensin receptor 1 (NTSR1) and receptor 2 (NTSR2) that belong to the G protein-coupled receptor superfamily. While studies on NTS and NTSR have been conducted mainly in mammalian systems, little is known about this ligand-receptor pair in nonmammalian species. Using a basic local alignment search tool combined with our previous identification of bullfrog Lithobates catesbeianus NTSR1 and NTSR2, we can define the evolutionary lineage of NTS and NTSR in vertebrates. Fish may have only one NTSR, which is orthologous to amphibian and mammalian NTSR1. Amphibian and mammalian species have two lineages of NTSR1 and NTSR2 subfamilies. While amphibian and mammalian NTSRs have overall structural similarity within the given subfamilies, they exhibit different pharmacological features and signal transduction pathways. This review will discuss the phylogenetic history of the G protein-coupled NTSRs, the structural features that may influence their pharmacological properties and signal transduction mechanisms, and the molecular interactions between NTSR1 and NTSR2 in vertebrates.</P>
Kim, Dong-Kyu,Cho, Eun Bee,Moon, Mi Jin,Park, Sumi,Hwang, Jong-Ik,Do Rego, Jean-Luc,Vaudry, Hubert,Seong, Jae Young Frontiers Research Foundation 2012 Frontiers in neuroscience Vol.6 No.-
<P>The neuropeptides gonadotropin-releasing hormone (GnRH) and kisspeptin (KiSS), and their receptors gonadotropin-releasing hormone receptor (GnRHR) and kisspeptin receptor (KiSSR) play key roles in vertebrate reproduction. Multiple paralogous isoforms of these genes have been identified in various vertebrate species. Two rounds of genome duplication in early vertebrates likely contributed to the generation of these paralogous genes. Genome synteny and phylogenetic analyses in a variety of vertebrate species have provided insights into the evolutionary origin of and relationship between paralogous genes. The paralogous forms of these neuropeptides and their receptors have coevolved to retain high selectivity of the ligand–receptor interaction. These paralogous forms have become subfunctionalized, neofunctionalized, or dysfunctionalized during evolution. This article reviews the evolutionary mechanism of GnRH/GnRHR and KiSS/KiSSR, and the fate of the duplicated paralogs in vertebrates.</P>
Kim, Dong-Kyu,Yun, Seongsik,Son, Gi Hoon,Hwang, Jong-Ik,Park, Cho Rong,Kim, Jae Il,Kim, Kyungjin,Vaudry, Hubert,Seong, Jae Young The Endocrine Society 2014 Endocrinology Vol.155 No.5
<P>The novel neuropeptide spexin (SPX) was discovered using bioinformatics. The function of this peptide is currently under investigation. Here, we identified SPX along with a second SPX gene (SPX2) in vertebrate genomes. Syntenic analysis and relocating SPXs and their neighbor genes on reconstructed vertebrate ancestral chromosomes revealed that SPXs reside in the near vicinity of the kisspeptin (KISS) and galanin (GAL) family genes on the chromosomes. Alignment of mature peptide sequences showed some extent of sequence similarity among the 3 peptide groups. Gene structure analysis indicated that SPX is more closely related to GAL than KISS. These results suggest that the SPX, GAL, and KISS genes arose through local duplications before 2 rounds (2R) of whole-genome duplication. Receptors of KISS and GAL (GAL receptor [GALR]) are phylogenetically closest among rhodopsin-like G protein-coupled receptors, and synteny revealed the presence of 3 distinct receptor families KISS receptor, GALR1, and GALR2/3 before 2R. Aligand-receptor interaction study showed that SPXs activate human, Xenopus, and zebrafish GALR2/3 family receptors but not GALR1, suggesting that SPXs are natural ligands for GALR2/3. Particularly, SPXs exhibited much higher potency toward GALR3 than GAL. Together, these results identify the coevolution of SPX/GAL/KISS ligand genes with their receptor genes. This study demonstrates the advantage of evolutionary genomics to explore the evolutionary relationship of a peptide gene family that arose before 2R by local duplications.</P>
Steroid Biosynthesis within the Frog Brain : A Model of Neuroendocrine Regulation
Rego, Jean-Luc Do,Seong, Jae Young,Burel, Delphine,Luu-The, Van,Larhammar, Dan,Tsutsui, Kazuyoshi,Pelletier, Georges,Tonon, Marie-Christine,Vaudry, Hubert Wiley (Blackwell Publishing) 2009 Annals of the New York Academy of Sciences Vol.1163 No.1
<P>There is now clear evidence that the brain, similar to the adrenal gland, gonads, and placenta, is a steroidogenic organ. Notably in the frog brain, the presence of various steroidogenic enzymes has been detected by immunohistochemistry in specific populations of neurons and/or glial cells. These steroidogenic enzymes are biologically active, as shown by the ability of brain tissue explants to convert [(3)H]pregnenolone into various radiolabeled steroids. The frog brain has also been extensively used as a model to study the mechanism of regulation of neurosteroidogenesis by neurotransmitters and neuropeptides. It has been demonstrated that the biosynthesis of neurosteroids is inhibited by gamma-aminobutyric acid (GABA), acting through GABA(A) receptors, and neuropeptide Y, acting through Y1 receptors, and is stimulated by the octadecaneuropeptide (ODN), acting through central-type benzodiazepine receptors, triakontatetraneuropeptide (TTN), acting through peripheral-type benzodiazepine receptors, and vasotocin, acting through V1a-like receptors. These data indicate that some of the neurophysiological effects of neurotransmitters and neuropeptides may be mediated through modulation of neurosteroid biosynthesis.</P>
Molecular evolution of multiple forms of kisspeptins and GPR54 receptors in vertebrates.
Lee, Yeo Reum,Tsunekawa, Kenta,Moon, Mi Jin,Um, Haet Nim,Hwang, Jong-Ik,Osugi, Tomohiro,Otaki, Naohito,Sunakawa, Yuya,Kim, Kyungjin,Vaudry, Hubert,Kwon, Hyuk Bang,Seong, Jae Young,Tsutsui, Kazuyoshi Association for the Study of Internal Secretions 2009 Endocrinology Vol.150 No.6
<P>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.</P>
Hwang, Jong-Ik,Moon, Mi Jin,Park, Sumi,Kim, Dong-Kyu,Cho, Eun Bee,Ha, Nui,Son, Gi Hoon,Kim, Kyungjin,Vaudry, Hubert,Seong, Jae Young Society for Molecular Biology and Evolution 2013 Molecular biology and evolution Vol.30 No.5
<P>In humans, the secretin-like G protein-coupled receptor (GPCR) family comprises 15 members with 18 corresponding peptide ligand genes. Although members have been identified in a large variety of vertebrate and nonvertebrate species, the origin and relationship of these proteins remain unresolved. To address this issue, we employed large-scale genome comparisons to identify genome fragments with conserved synteny and matched these fragments to linkage groups in reconstructed early gnathostome ancestral chromosomes (<I>GAC</I>). This genome comparison revealed that most receptor and peptide genes were clustered in three <I>GAC</I> linkage groups and suggested that the ancestral forms of five peptide subfamilies (corticotropin-releasing hormone-like, calcitonin-like, parathyroid hormone-like, glucagon-like, and growth hormone-releasing hormone-like) and their cognate receptor families emerged through tandem local gene duplications before two rounds (2R) of whole-genome duplication. These subfamily genes have, then, been amplified by 2R whole-genome duplication, followed by additional local duplications and gene loss prior to the divergence of land vertebrates and teleosts. This study delineates a possible evolutionary scenario for whole secretin-like peptide and receptor family members and may shed light on evolutionary mechanisms for expansion of a gene family with a large number of paralogs.</P>
Do Rego, Jean Luc,Seong, Jae Young,Burel, Delphine,Leprince, Jerô,me,Luu-The, Van,Tsutsui, Kazuyoshi,Tonon, Marie-Christine,Pelletier, Georges,Vaudry, Hubert Elsevier 2009 Frontiers in neuroendocrinology Vol.30 No.3
<P><B>Abstract</B></P><P>Neuroactive steroids synthesized in neuronal tissue, referred to as neurosteroids, are implicated in proliferation, differentiation, activity and survival of nerve cells. Neurosteroids are also involved in the control of a number of behavioral, neuroendocrine and metabolic processes such as regulation of food intake, locomotor activity, sexual activity, aggressiveness, anxiety, depression, body temperature and blood pressure. In this article, we summarize the current knowledge regarding the existence, neuroanatomical distribution and biological activity of the enzymes responsible for the biosynthesis of neurosteroids in the brain of vertebrates, and we review the neuronal mechanisms that control the activity of these enzymes. The observation that the activity of key steroidogenic enzymes is finely tuned by various neurotransmitters and neuropeptides strongly suggests that some of the central effects of these neuromodulators may be mediated via the regulation of neurosteroid production.</P>