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Title
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Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in **Caenorhabditis elegans**
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Author
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Abstract
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| 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 (EC(50) = 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 Ca(2+) 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. |
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Language
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English
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Source (journal)
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Proceedings of the National Academy of Sciences of the United States of America. - Washington, D.C.
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Publication
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Washington, D.C.
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2009
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ISSN
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0027-8424
[Print]
1091-6490
[Online]
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DOI
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10.1073/PNAS.0809881106
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Volume/pages
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106
:5
(2009)
, p. 1642-1647
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ISI
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000263074600063
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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