Endocannabinoids in Caenorhabditis elegans are essential for the mobilization of cholesterol from internal reserves

Proper cholesterol transport is crucial for the functionality of cells. In C. elegans, certain cholesterol derivatives called dafachronic acids (DAs) govern the entry into diapause. In their absence, worms form a developmentally arrested dauer larva. Thus, cholesterol transport to appropriate places...

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Detalles Bibliográficos
Autores: Galles, Celina, Prez, Gastón Matías, Penkov, Sider, Boland, Sebastian, Porta, Exequiel Oscar Jesús, Altabe, Silvia Graciela, Labadie, Guillermo Roberto, Schmidt, Ulrike, Knölker, Hans Joachim, Kurzchalia, Teymuras V., de Mendoza, Diego
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/92612
Acceso en línea:http://hdl.handle.net/11336/92612
Access Level:acceso abierto
Palabra clave:ENDOCANNABONOIDS
CAENORHABDITIS ELEGANS
NEUROCHEMISTRY
CHOLESTEROL
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Descripción
Sumario:Proper cholesterol transport is crucial for the functionality of cells. In C. elegans, certain cholesterol derivatives called dafachronic acids (DAs) govern the entry into diapause. In their absence, worms form a developmentally arrested dauer larva. Thus, cholesterol transport to appropriate places for DA biosynthesis warrants the reproductive growth. Recently, we discovered a novel class of glycosphingolipids, PEGCs, required for cholesterol mobilization/transport from internal storage pools. Here, we identify other components involved in this process. We found that strains lacking polyunsaturated fatty acids (PUFAs) undergo increased dauer arrest when grown without cholesterol. This correlates with the depletion of the PUFA-derived endocannabinoids 2-arachidonoyl glycerol and anandamide. Feeding of these endocannabinoids inhibits dauer formation caused by PUFAs deficiency or impaired cholesterol trafficking (e.g. in Niemann-Pick C1 or DAF-7/TGF-β mutants). Moreover, in parallel to PEGCs, endocannabinoids abolish the arrest induced by cholesterol depletion. These findings reveal an unsuspected function of endocannabinoids in cholesterol trafficking regulation.

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