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

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 Hauge
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 biogenèse 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 A.
dc.contributor.authorGUIXA-GONZALEZ, Ramon
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorALVES, Isabel
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorTRIFILIEFF, Pierre
dc.date.accessioned2023-05-31T10:08:53Z
dc.date.available2023-05-31T10:08:53Z
dc.date.issued2023-01-06
dc.identifier.issn1476-5578en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182385
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.sponsorshipInitiative d'excellence de l'Université de Bordeaux - ANR-10-IDEX-0003en_US
dc.description.sponsorshipImpact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivation - ANR-16-CE16-0022en_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.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 signaling
dc.title.alternativeMol Psychiatryen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41380-022-01928-6en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed36604603en_US
bordeaux.journalMolecular Psychiatryen_US
bordeaux.page1-10en_US
bordeaux.hal.laboratoriesNutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.institutionCNRS
bordeaux.institutionBordeaux INP
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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=2023-01-06&rft.spage=1-10&rft.epage=1-10&rft.eissn=1476-5578&rft.issn=1476-5578&rft.au=JOBIN,%20Marie-Lise&DE%20SMEDT-PEYRUSSE,%20Veronique&DUCROCQ,%20Fabien&BACCOUCH,%20Rim&OUMMADI,%20Asma&rft.genre=article


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