Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans

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dc.citation.titlePLoS Geneticses
dc.citation.volume11
dc.creatorHernández Cravero, Bruno
dc.creatorGallinoI, Sofía
dc.creatorFlorman, Jeremy
dc.creatorVranych, Cecilia V.
dc.creatorDiaz, Philippe
dc.creatorElgoyhen, Ana Belén
dc.creatorAlkemaI, Mark J.
dc.creatorDe Mendoza, Diego
dc.date.accessioned2022-12-16T14:27:19Z
dc.date.available2022-12-16T14:27:19Z
dc.date.issued2022-11
dc.descriptionThe nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is critical. Previously, we demonstrated that the endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) plays a key role in C. elegans since it modulates sterol mobilization. However, the mechanism remains unknown. Here we show that mutations in the ocr-2 and osm-9 genes, coding for transient receptors potential V (TRPV) ion channels, dramatically reduce the effect of 2-AG in cholesterol mobilization. Through genetic analysis in combination with the rescue of larval arrest induced by sterol starvation, we found that the insulin/IGF-1signaling (IIS) pathway and UNC-31/CAPS, a calcium-activated regulator of neural dense-core vesicles release, are essential for 2-AG-mediated stimulation of cholesterol mobilization. These findings indicate that 2-AG-dependent cholesterol trafficking requires the release of insulin peptides and signaling through the DAF-2 insulin receptor. These results suggest that 2-AG acts as an endogenous modulator of TRPV signal transduction to control intracellular sterol trafficking through modulation of the IGF-1 signaling pathwayes
dc.description.filFil: Hernández Cravero, Bruno. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.es
dc.description.filFil: Gallino, Sofía. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Fisiología y Genética de la Audición (INGEBI-CONICET); Argentina.es
dc.description.filFil: Florman, Jeremy. University of Massachusetts Medical School. Department of Neurobiology; United States.es
dc.description.filFil: Vranych, Cecilia V. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.es
dc.description.filFil: Diaz, Philippe. University of Montana. Department of Biomedical and Pharmaceutical Sciences; United States.es
dc.description.filFil: Elgoyhen, Ana Belén. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Laboratorio de Fisiología y Genética de la Audición (INGEBI-CONICET); Argentina.es
dc.description.filFil: AlkemaI, Mark J. University of Massachusetts Medical School. Department of Neurobiology; United States.es
dc.description.filFil: De Mendoza, Diego. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Laboratorio de Fisiología Microbiana (IBR-CONICET); Argentina.es
dc.description.sponsorshipNIH Office of Research Infrastructure Programs: P40 OD010440
dc.formatapplication/pdf
dc.format.extent1-22es
dc.identifier.issn1553-7390es
dc.identifier.urihttp://hdl.handle.net/2133/25036
dc.language.isoenges
dc.publisherPublic Library of Sciencees
dc.relation.publisherversionhttps://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010346
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pgen.1010346
dc.rightsopenAccesses
dc.rights.holderHernández Cravero, Brunoes
dc.rights.holderGallinoI, Sofíaes
dc.rights.holderFlorman, Jeremyes
dc.rights.holderVranych, Cecilia V.es
dc.rights.holderDiaz, Philippees
dc.rights.holderElgoyhen, Ana Belénes
dc.rights.holderAlkemaI, Mark J.es
dc.rights.holderDe Mendoza, Diegoes
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution 4.0 International (CC BY 4.0)es
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectAnimalses
dc.subjectCaenorhabditis eleganses
dc.subjectCannabinoidses
dc.subjectCholesteroles
dc.subjectInsulines
dc.subjectSterolses
dc.titleCannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. eleganses
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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(FBIOyF) Departamento de Química Orgánica - Artículos