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

The 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-arachido...

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Detalles Bibliográficos
Autores principales: Hernández Cravero, Bruno, GallinoI, Sofía, Florman, Jeremy, Vranych, Cecilia, Diaz, Philippe, Elgoyhen, Ana Belén, AlkemaI, Mark J., De Mendoza, Diego
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: Public Library of Science 2022
Materias:
Animals
Caenorhabditis elegans
Cannabinoids
Cholesterol
Insulin
Sterols
Acceso en línea:http://hdl.handle.net/2133/25036
http://hdl.handle.net/2133/25036
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-25036
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
topic Animals
Caenorhabditis elegans
Cannabinoids
Cholesterol
Insulin
Sterols
spellingShingle Animals
Caenorhabditis elegans
Cannabinoids
Cholesterol
Insulin
Sterols
Hernández Cravero, Bruno
GallinoI, Sofía
Florman, Jeremy
Vranych, Cecilia
Diaz, Philippe
Elgoyhen, Ana Belén
AlkemaI, Mark J.
De Mendoza, Diego
Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
topic_facet Animals
Caenorhabditis elegans
Cannabinoids
Cholesterol
Insulin
Sterols
description The 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 pathway
format article
artículo
publishedVersion
author Hernández Cravero, Bruno
GallinoI, Sofía
Florman, Jeremy
Vranych, Cecilia
Diaz, Philippe
Elgoyhen, Ana Belén
AlkemaI, Mark J.
De Mendoza, Diego
author_facet Hernández Cravero, Bruno
GallinoI, Sofía
Florman, Jeremy
Vranych, Cecilia
Diaz, Philippe
Elgoyhen, Ana Belén
AlkemaI, Mark J.
De Mendoza, Diego
author_sort Hernández Cravero, Bruno
title Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
title_short Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
title_full Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
title_fullStr Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
title_full_unstemmed Cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in C. elegans
title_sort cannabinoids activate the insulin pathway to modulate mobilization of cholesterol in c. elegans
publisher Public Library of Science
publishDate 2022
url http://hdl.handle.net/2133/25036
http://hdl.handle.net/2133/25036
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