Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. Export

@article{citeulike:4908115, 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 (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 Galpha(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.}, author = {Lindemans, M. and Liu, F. and Janssen, T. and Husson, S. J. and Mertens, I. and G\"{a}de, G. and Schoofs, L.}, citeulike-article-id = {4908115}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0809881106}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19164555}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19164555}, day = {3}, doi = {10.1073/pnas.0809881106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {adipokinetic, c, elegans, gnrh, hormone, receptor}, month = {February}, number = {5}, pages = {1642--1647}, posted-at = {2009-06-19 15:22:48}, priority = {0}, title = {Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans.}, url = {http://dx.doi.org/10.1073/pnas.0809881106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4908115 L3 - citeulike-article-id:4908115 N2 - 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 Galpha(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. IS - 5 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 1091-6490 EP - 1647 TI - Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. VL - 106 SP - 1642 KW - adipokinetic KW - c KW - elegans KW - gnrh KW - hormone KW - receptor AU - Lindemans, M AU - Liu, F AU - Janssen, T AU - Husson, SJ AU - Mertens, I AU - Gäde, G AU - Schoofs, L PY - 2009/02/03/ UR - http://dx.doi.org/10.1073/pnas.0809881106 ER -