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

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dc.contributor.authorLindemans, M
dc.contributor.authorLiu, F
dc.contributor.authorJanssen, T
dc.contributor.authorHusson, S J
dc.contributor.authorMertens, I
dc.contributor.authorGäde, G
dc.contributor.authorSchoofs, L
dc.date.accessioned2021-10-08T07:15:54Z
dc.date.available2021-10-08T07:15:54Z
dc.date.issued2009
dc.description.abstractIn 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 Gαq 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.
dc.identifier.apacitationLindemans, M., Liu, F., Janssen, T., Husson, S. J., Mertens, I., Gäde, G., & Schoofs, L. (2009). Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. <i>Proceedings of the National Academy of Sciences of the United States of America</i>, 106(5), 1642 - 1647. http://hdl.handle.net/11427/34720en_ZA
dc.identifier.chicagocitationLindemans, M, F Liu, T Janssen, S J Husson, I Mertens, G Gäde, and L Schoofs "Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans." <i>Proceedings of the National Academy of Sciences of the United States of America</i> 106, 5. (2009): 1642 - 1647. http://hdl.handle.net/11427/34720en_ZA
dc.identifier.citationLindemans, M., Liu, F., Janssen, T., Husson, S.J., Mertens, I., Gäde, G. & Schoofs, L. 2009. Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. <i>Proceedings of the National Academy of Sciences of the United States of America.</i> 106(5):1642 - 1647. http://hdl.handle.net/11427/34720en_ZA
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.ris TY - Journal Article AU - Lindemans, M AU - Liu, F AU - Janssen, T AU - Husson, S J AU - Mertens, I AU - Gäde, G AU - Schoofs, L AB - 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 Gαq 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. DA - 2009 DB - OpenUCT DP - University of Cape Town IS - 5 J1 - Proceedings of the National Academy of Sciences of the United States of America LK - https://open.uct.ac.za PY - 2009 SM - 0027-8424 SM - 0744-2831 SM - 1091-6490 T1 - Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans TI - Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans UR - http://hdl.handle.net/11427/34720 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34720
dc.identifier.vancouvercitationLindemans M, Liu F, Janssen T, Husson SJ, Mertens I, Gäde G, et al. Adipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(5):1642 - 1647. http://hdl.handle.net/11427/34720.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Biological Sciences
dc.publisher.facultyFaculty of Science
dc.sourceProceedings of the National Academy of Sciences of the United States of America
dc.source.journalissue5
dc.source.journalvolume106
dc.source.pagination1642 - 1647
dc.source.urihttps://dx.doi.org/10.1073/pnas.0809881106
dc.subject.otherAmino Acid Sequence
dc.subject.otherAnimals
dc.subject.otherBase Sequence
dc.subject.otherCaenorhabditis elegans
dc.subject.otherCarbohydrate Metabolism
dc.subject.otherCell Line
dc.subject.otherCloning, Molecular
dc.subject.otherDNA Primers
dc.subject.otherGene Knockdown Techniques
dc.subject.otherGene Silencing
dc.subject.otherHumans
dc.subject.otherInsect Hormones
dc.subject.otherMolecular Sequence Data
dc.subject.otherOligopeptides
dc.subject.otherOvum
dc.subject.otherPyrrolidonecarboxylic Acid
dc.titleAdipokinetic hormone signaling through the gonadotropin-releasing hormone receptor modulates egg-laying in Caenorhabditis elegans
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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