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Title: | Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans | Authors: | Lindemans, Marleen LIU, Feng Janssen, Tom Husson, Steven J. Mertens, Inge Gaede, Gerd Schoofs, Liliane |
Issue Date: | 2009 | Publisher: | NATL ACAD SCIENCES | Source: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(5). p. 1642-1647 | Abstract: | In mammals, hypothalamic gonadotropin-releasing hormone (GnRH) is a neuropeptide that stimulates the release of gonadotropins from the anterior pituitary. The existence of a putative functional equivalent of this reproduction axis in protostomian invertebrates has been a matter of debate. In this study, the ligand for the GnRH receptor in the nematode Caenorhabditis elegans (Ce-GnRHR) was found using a bioinformatics approach. The peptide and its precursor are reminiscent of both insect adipokinetic hormones and GnRH-preprohormone precursors from tunicates and higher vertebrates. We cloned the AKH-GnRH-like preprohormone and the Ce-GnRHR and expressed the GPCR in HEK293T cells. The GnRHR was activated by the C. elegans AKH-GnRH-like peptide (EC50 = 150 nM) and by Drosophila AKH and other nematode AKH-GnRHs that we found in EST databases. Analogous to both insect AKH receptor and vertebrate GnRH receptor signaling, Ce-AKH-GnRH activated its receptor through a G alpha(q) protein with Ca2+ as a second messenger. Gene silencing of Ce-GnRHR, Ce-AKH-GnRH, or both resulted in a delay in the egg-laying process, comparable to a delay in puberty in mammals lacking a normal dose of GnRH peptide or with a mutated GnRH precursor or receptor gene. The present data support the view that the AKH-GnRH signaling system probably arose very early in metazoan evolution and that its role in reproduction might have been developed before the divergence of protostomians and deuterostomians. | Notes: | [Lindemans, Marleen; Janssen, Tom; Husson, Steven J.; Mertens, Inge; Schoofs, Liliane] Katholieke Univ Leuven, Funct Genom & Prote Res Unit, B-3000 Louvain, Belgium. [Liu, Feng] Hasselt Univ, Transportat Res Inst, Data Anal & Modeling Grp, B-3590 Diepenbeek, Belgium. [Gaede, Gerd] Univ Cape Town, Dept Zool, ZA-7701 Rondebosch, South Africa. | Keywords: | C. elegans; G protein-coupled receptor; molecular evolution; neuropeptide; neuroendocrinology | Document URI: | http://hdl.handle.net/1942/9284 | ISSN: | 0027-8424 | e-ISSN: | 1091-6490 | DOI: | 10.1073/pnas.0809881106 | ISI #: | 000263074600063 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2010 |
Appears in Collections: | Research publications |
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