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Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signalling

dc.rights.licenseopenen_US
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorJOBIN, Marie-Lise
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDE SMEDT-PEYRUSSE, Veronique
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorDUCROCQ, Fabien
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBACCOUCH, Rim
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorOUMMADI, Asma
dc.contributor.authorPEDERSEN, Maria
dc.contributor.authorMEDEL-LACRUZ, Brian
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorANGELO, Maria-Florencia
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorVILLETTE, Sandrine
hal.structure.identifierLaboratoire de biogenèse membranaire [LBM]
dc.contributor.authorVAN DELFT, Pierre
hal.structure.identifierLaboratoire de Bioénergie Membranaire [LBM]
dc.contributor.authorFOUILLEN, Laetitia
hal.structure.identifierLaboratoire de biogenèse membranaire [LBM]
dc.contributor.authorMONGRAND, Sébastien
dc.contributor.authorSELENT, Jana
dc.contributor.authorTOLENTINO-CORTEZ, Tarson
dc.contributor.authorBARREDA-GOMEZ, Gabriel
dc.contributor.authorGREGOIRE, Stephane
dc.contributor.authorMASSON, Elodie
dc.contributor.authorDURROUX, Thierry
dc.contributor.authorJAVITCH, Jonathan
dc.contributor.authorGUIXA-GONZALEZ, Ramon
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorALVES, Isabel D.
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorTRIFILIEFF, Pierre
dc.date.accessioned2024-04-23T10:34:14Z
dc.date.available2024-04-23T10:34:14Z
dc.date.issued2023-05
dc.identifier.issn1359-4184en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/199278
dc.description.abstractEnIncreasing evidence supports a relationship between lipid metabolism and mental health. In particular, the biostatus of polyunsaturated fatty acids (PUFAs) correlates with some symptoms of psychiatric disorders, as well as the efficacy of pharmacological treatments. Recent findings highlight a direct association between brain PUFA levels and dopamine transmission, a major neuromodulatory system implicated in the etiology of psychiatric symptoms. However, the mechanisms underlying this relationship are still unknown. Here we demonstrate that membrane enrichment in the n-3 PUFA docosahexaenoic acid (DHA), potentiates ligand binding to the dopamine D2 receptor (D2R), suggesting that DHA acts as an allosteric modulator of this receptor. Molecular dynamics simulations confirm that DHA has a high preference for interaction with the D2R and show that membrane unsaturation selectively enhances the conformational dynamics of the receptor around its second intracellular loop. We find that membrane unsaturation spares G protein activity but potentiates the recruitment of β-arrestin in cells. Furthermore, in vivo n-3 PUFA deficiency blunts the behavioral effects of two D2R ligands, quinpirole and aripiprazole. These results highlight the importance of membrane unsaturation for D2R activity and provide a putative mechanism for the ability of PUFAs to enhance antipsychotic efficacy.
dc.description.sponsorshipDéveloppement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovationen_US
dc.description.sponsorshipImpact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivationen_US
dc.description.sponsorshipRole du biostatus en acides gras polyinsaturés dans les troubles de contrôle exécutifen_US
dc.description.sponsorshipImpacte de la poly-insaturation phospholipidique dans la dynamique, l'activation et la signalisation du récepteur Dopamine D2en_US
dc.description.sponsorshipInitiative d'excellence de l'Université de Bordeaux - ANR-10-IDEX-0003en_US
dc.language.isoENen_US
dc.subject.enCell biology
dc.subject.enPsychiatric disorders
dc.title.enImpact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signalling
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-022-01928-6en_US
dc.subject.halSciences du Vivant [q-bio]/Biologie cellulaireen_US
dc.subject.halSciences cognitives/Neurosciencesen_US
dc.subject.halSciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologieen_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.page1960-1969en_US
bordeaux.volume28en_US
bordeaux.hal.laboratoriesCBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04286162
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Psychiatry&rft.date=2023-05&rft.volume=28&rft.issue=5&rft.spage=1960-1969&rft.epage=1960-1969&rft.eissn=1359-4184&rft.issn=1359-4184&rft.au=JOBIN,%20Marie-Lise&DE%20SMEDT-PEYRUSSE,%20Veronique&DUCROCQ,%20Fabien&BACCOUCH,%20Rim&OUMMADI,%20Asma&rft.genre=article


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