Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling
dc.rights.license | open | en_US |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | JOBIN, Marie-Lise | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | DE SMEDT-PEYRUSSE, Veronique | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | DUCROCQ, Fabien | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | BACCOUCH, Rim | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | OUMMADI, Asma | |
dc.contributor.author | PEDERSEN, Maria Hauge | |
dc.contributor.author | MEDEL-LACRUZ, Brian | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | ANGELO, Maria-Florencia | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | VILLETTE, Sandrine | |
hal.structure.identifier | Laboratoire de biogenèse membranaire [LBM] | |
dc.contributor.author | VAN DELFT, Pierre | |
hal.structure.identifier | Laboratoire de biogenèse membranaire [LBM] | |
dc.contributor.author | FOUILLEN, Laetitia | |
hal.structure.identifier | Laboratoire de biogenèse membranaire [LBM] | |
dc.contributor.author | MONGRAND, Sébastien | |
dc.contributor.author | SELENT, Jana | |
dc.contributor.author | TOLENTINO-CORTEZ, Tarson | |
dc.contributor.author | BARREDA-GOMEZ, Gabriel | |
dc.contributor.author | GREGOIRE, Stephane | |
dc.contributor.author | MASSON, Elodie | |
dc.contributor.author | DURROUX, Thierry | |
dc.contributor.author | JAVITCH, Jonathan A. | |
dc.contributor.author | GUIXA-GONZALEZ, Ramon | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | ALVES, Isabel | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | TRIFILIEFF, Pierre | |
dc.date.accessioned | 2023-05-31T10:08:53Z | |
dc.date.available | 2023-05-31T10:08:53Z | |
dc.date.issued | 2023-01-06 | |
dc.identifier.issn | 1476-5578 | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/182385 | |
dc.description.abstractEn | Increasing 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.sponsorship | Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation | en_US |
dc.description.sponsorship | Initiative d'excellence de l'Université de Bordeaux - ANR-10-IDEX-0003 | en_US |
dc.description.sponsorship | Impact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivation | en_US |
dc.description.sponsorship | Role du biostatus en acides gras polyinsaturés dans les troubles de contrôle exécutif | en_US |
dc.description.sponsorship | Impacte de la poly-insaturation phospholipidique dans la dynamique, l'activation et la signalisation du récepteur Dopamine D2 | en_US |
dc.language.iso | EN | en_US |
dc.subject.en | Cell biology | |
dc.subject.en | Psychiatric disorders | |
dc.title.en | Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling | |
dc.title.alternative | Mol Psychiatry | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1038/s41380-022-01928-6 | en_US |
dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
dc.identifier.pubmed | 36604603 | en_US |
bordeaux.journal | Molecular Psychiatry | en_US |
bordeaux.page | 1-10 | en_US |
bordeaux.hal.laboratories | NutriNeuro (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286 | en_US |
bordeaux.institution | Université de Bordeaux | en_US |
bordeaux.institution | INRAE | en_US |
bordeaux.institution | CNRS | |
bordeaux.institution | Bordeaux INP | |
bordeaux.peerReviewed | oui | en_US |
bordeaux.inpress | non | en_US |
hal.export | false | |
dc.rights.cc | Pas de Licence CC | en_US |
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