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

2023-01-06 16:53:09 By : Ms. jenny wu

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Molecular Psychiatry (2023 )Cite this article Finasteride Powder

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

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.

This is a preview of subscription content, access via your institution

Get full journal access for 1 year

All prices are NET prices. VAT will be added later in the checkout. Tax calculation will be finalised during checkout.

Get time limited or full article access on ReadCube.

All prices are NET prices.

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. All MD simulation trajectories generated in this study can be visualized and inspected through the GPCRmd online resource [99]; GPCRmd IDs: 1239, 1240, 1241, 1242, and 1243.

Rohrbough J, Broadie K. Lipid regulation of the synaptic vesicle cycle. Nat Rev Neurosci. 2005;6:139–50.

Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15:771–85.

Messamore E, McNamara RK. Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: rationale and implementation. Lipids Health Dis. 2016;15:1–13.

Ohi K, Ursini G, Li M, Shin JH, Ye T, Chen Q, et al. DEGS2 polymorphism associated with cognition in schizophrenia is associated with gene expression in brain. Transl Psychiatry. 2015;5:1–6.

Shimamoto C, Ohnishi T, Maekawa M, Watanabe A, Ohba H, Arai R, et al. Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies. Hum Mol Genet. 2014;23:6495–511.

Beltz BS, Tlusty MF, Benton JL, Sandeman DC. Omega-3 fatty acids upregulate adult neurogenesis. Neurosci Lett. 2007;415:154–8.

Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004;90:979–88.

Harayama T, Riezman H. Understanding the diversity of membrane lipid composition. Nat Rev Mol Cell Biol. 2018;19:281–96.

Dawaliby R, Trubbia C, Delporte C, Masureel M, Van Antwerpen P, Kobilka BK, et al. Allosteric regulation of G protein-coupled receptor activity by phospholipids. Nat Chem Biol. 2016;12:35–9.

Duncan AL, Song W, Sansom MSP. Lipid-dependent regulation of ion channels and g protein-coupled receptors: Insights from structures and simulations. Annu Rev Pharm Toxicol. 2020;60:31–50.

Whitton AE, Treadway MT, Pizzagalli DA. Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry. 2015;28:7–12.

Bondi CO, Taha AY, Tock JL, Totah NKB, Cheon Y, Torres GE, et al. Adolescent behavior and dopamine availability are uniquely sensitive to dietary omega-3 fatty acid deficiency. Biol Psychiatry. 2014;75:38–46.

Chalon S. Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Ess Fat Acids. 2006;75:259–69.

Ducrocq F, Walle R, Contini A, Oummadi A, Caraballo B, van der Veldt S, et al. Causal Link between n-3 polyunsaturated fatty acid deficiency and motivation deficits. Cell Metab. 2020;31:755–72.

Litman BJ, Mitchell DC. A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids. 1996;31:193–7.

Mitchell DC, Niu SL, Litman BJ. Enhancement of G protein-coupled signaling by DHA phospholipids. Lipids. 2003;38:437–43.

Salem N, Litman B, Kim H, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001;36:945–59.

Feller SE, Gawrisch K, Woolf TB. Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid. J Am Chem Soc. 2003;125:4434–5.

Pitman MC, Grossfield A, Suits F, Feller SE. Role of cholesterol and polyunsaturated chains in lipid-protein interactions: molecular dynamics simulation of rhodopsin in a realistic membrane environment. J Am Chem Soc. 2005;127:4576–7.

Guixà-González R, Javanainen M, Gómez-Soler M, Cordobilla B, Domingo JC, Sanz F, et al.Membrane omega-3 fatty acids modulate the oligomerisation kinetics of adenosine A2A and dopamine D2 receptors.Sci Rep. 2016;6:1–13.

Javanainen M, Enkavi G, Guixà-Gonzaléz R, Kulig W, Martinez-Seara H, Levental I, et al.Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions.PLoS Comput Biol. 2019;15:1–16.

Polozova A, Litman BJ. Cholesterol dependent recruitment of di22:6-PC by a G protein-coupled receptor into lateral domains. Biophys J. 2000;79:2632–43.

De Smedt-Peyrusse V, Sargueil F, Moranis A, Harizi H, Mongrand S, Layé S. Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization. J Neurochem. 2008;105:296–307.

Alves ID, Lecomte S. Study of G-protein coupled receptor signaling in membrane environment by plasmon waveguide resonance. Acc Chem Res. 2019;52:1059–67.

Salamon Z, Macleod HA, Tollin G. Coupled plasmon-waveguide resonators: a new spectroscopic tool for probing proteolipid film structure and properties. Biophys J. 1997;73:2791–7.

Mueller P, Rudin DO. Resting and action potentials in experimental bimolecular lipid membranes. J Theor Biol. 1968;18:222–58.

Harté E, Maalouli N, Shalabney A, Texier E, Berthelot K, Lecomte S, et al. Probing the kinetics of lipid membrane formation and the interaction of a nontoxic and a toxic amyloid with plasmon waveguide resonance. Chem Commun. 2014;50:4168–71.

Perez JB, Segura JM, Abankwa D, Piguet J, Martinez KL, Vogel H. Monitoring the diffusion of single heterotrimeric G proteins in supported cell-membrane sheets reveals their partitioning into microdomains. J Mol Biol. 2006;363:918–30.

Salamon Z, Tollin G. Graphical analysis of mass and anisotropy changes observed by plasmon-waveguide resonance spectroscopy can provide useful insights into membrane protein function. Biophys J. 2004;86:2508–16.

Fernández R, Garate J, Tolentino-Cortez T, Herraiz A, Lombardero L, Ducrocq F, et al. Microarray and mass spectrometry-based methodology for lipid profiling of tissues and cell cultures. Anal Chem. 2019;91:15967–73.

Joffre C, Grégoire S, De Smedt V, Acar N, Bretillon L, Nadjar A, et al. Modulation of brain PUFA content in different experimental models of mice. Prostaglandins Leukot Ess Fat Acids. 2016;114:1–10.

Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957;226:497–509.

Morrison WR, Smith LM. Preparation of fatty acid methyl esters and dimethylacetals from lipids. J Lipid Res. 1964;5:600–8.

Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14:33–8.

Webb B, Sali A. Comparative protein structure modeling using MODELLER. Curr Protoc Bioinforma. 2016;54:5.6.1-5.6.37.

Mayol E, Garcia-Recio A, Tiemann JKS, Hildebrand PW, Guixa-Gonzalez R, Olivella M, et al.Homolwat: a web server tool to incorporate 'homologous' water molecules into gPCR structures.Nucleic Acids Res.2020;48:W54–W59.

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2009;31:455–61.

Jo S, Kim T, Im W. Automated builder and database of protein/membrane complexes for molecular dynamics simulations. PLoS One. 2007;2:e880.

Wu EL, Cheng X, Jo S, Rui H, Song KC, Dávila-Contreras EM, et al.CHARMM-GUI membrane builder towards realistic biological membrane simulations.J Comput Chem. 2014;35:1997–2004.

Harvey MJ, Giupponi G, De Fabritiis G. ACEMD: Accelerating biomolecular dynamics in the microsecond time scale. J Chem Theory Comput. 2009;5:1632–9.

Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, De Groot BL, et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat Methods. 2016;14:71–3.

Doerr S, Harvey MJ, Noé F, De Fabritiis G. HTMD: high-throughput molecular dynamics for molecular discovery. J Chem Theory Comput. 2016;12:1845–52.

Stone JE, Vandivort KL, Schulten K. GPU-accelerated molecular visualization on petascale supercomputing platforms. In: Proceedings of the 8th International Workshop on Ultrascale Visualization, 2013. Association for Computing Machinery, New York, NY, USA, Article 6, 1–8.

Wickham H. Ggplot2: elegant graphics for data analysis. Springer-Verlag New York, 2016.

Song W, Corey RA, Ansell TB, Cassidy CK, Horrell MR, Duncan AL, et al. PyLipID: a python package for analysis of protein−lipid interactions from molecular dynamics simulations. J Chem Theory Comput. 2022;18:31.

Lin J. Divergence measures based on the Shannon entropy. IEEE Trans Inf Theory. 1991;37:145–51.

Vögele M, Thomson NJ, Truong ST, McAvity J, Zachariae U, Dror RO. Systematic Analysis of Biomolecular Conformational Ensembles with PENSA. arXiv:2212.02714v1 [q-bio.BM].

Stillwell W, Wassall SR. Docosahexaenoic acid: membrane properties of a unique fatty acid. Chem Phys Lipids. 2003;126:1–27.

Alves I, Park C, Hruby V. Plasmon resonance methods in GPCR signaling and other membrane events. Curr Protein Pept Sci. 2005;6:293–312.

De Jong LAA, Grünewald S, Franke JP, Uges DRA, Bischoff R. Purification and characterization of the recombinant human dopamine D2S receptor from Pichia pastoris. Protein Expr Purif. 2004;33:176–84.

Malmberg A, Mohell N. Characterization of [3H]quinpirole binding to human dopamine D(2A) and D3 receptors: effects of ions and guanine nucleotides. J Pharm Exp Ther. 1995;274:790–7.

Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R, Brabet I, et al. Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol. 2010;6:587–94.

Maurel D, Comps-Agrar L, Brock C, Rives ML, Bourrier E, Ayoub MA, et al. Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies: application to GPCR oligomerization. Nat Methods. 2008;5:561–7.

Alves ID, Cowell SM, Salamon Z, Devanathan S, Tollin G, Hruby VJ. Different structural states of the proteolipid membrane are produced by ligand binding to the human δ-opioid receptor as shown by plasmon-waveguide resonance spectroscopy. Mol Pharm. 2004;69:1248–57.

Alves ID, Delaroche D, Mouillac B, Salamon Z, Tollin G, Hruby VJ, et al. The two NK-1 binding sites correspond to distinct, independent, and non-interconvertible receptor conformational states as confirmed by plasmon-waveguide resonance spectroscopy. Biochemistry. 2006;45:5309–18.

Boyé K, Pujol N, D Alves I, Chen YP, Daubon T, Lee YZ, et al. The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors. Nat Commun. 2017;8:1–20.

Boyé K, Billottet C, Pujol N, Alves ID, Bikfalvi A. Ligand activation induces different conformational changes in CXCR3 receptor isoforms as evidenced by plasmon waveguide resonance (PWR). Sci Rep. 2017;7:1–11.

Lee J, Welti R, Roth M, Schapaugh WT, Li J, Trick HN. Enhanced seed viability and lipid compositional changes during natural ageing by suppressing phospholipase Dα in soybean seed. Plant Biotechnol J. 2012;10:164–73.

Takahashi D, Imai H, Kawamura Y, Uemura M. Lipid profiles of detergent resistant fractions of the plasma membrane in oat and rye in association with cold acclimation and freezing tolerance. Cryobiology. 2016;72:123–34.

Beaulieu JM, Gainetdinov RR, Caron MG. The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharm Sci. 2007;28:166–72.

Lafourcade M, Larrieu T, Mato S, Duffaud A, Sepers M, Matthias I, et al.Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions.Nat Neurosci.2011;14:345–50.

Mizumura T, Kondo K, Kurita M, Kofuku Y, Natsume M, Imai S, et al. Activation of adenosine A2A receptor by lipids from docosahexaenoic acid revealed by NMR. Sci Adv. 2020;6:8544–62.

Grossfield A, Feller SE, Pitman MC. A role for interactions in the modulation of rhodopsin by ω-3 polyunsaturated lipids. Proc Natl Acad Sci USA. 2006;103:4888–93.

Soubias O, Teague WE, Gawrisch K. Evidence for specificity in lipid-rhodopsin interactions. J Biol Chem. 2006;281:33233–41.

Guixà-González R, Albasanz JL, Rodriguez-Espigares I, Pastor M, Sanz F, Martí-Solano M, et al.Membrane cholesterol access into a G-protein-coupled receptor.Born Commun.2017;8:1–12.

Carrillo-Tripp M, Feller SE. Evidence for a mechanism by which ω-3 polyunsaturated lipids may affect membrane protein function. Biochemistry. 2005;44:10164–9.

Bruno MJ, Koeppe RE, Andersen OS.Docosahexaenoic acid ages bilayer elastic properties.Proc Natl Acad Sci USA.2007;104:9638–43.

Caires R, Sierra-Valdez FJ, Millet JRM, Herwig JD, Roan E, Vásquez V, et al. Omega-3 fatty acids modulate TRPV4 function through plasma membrane remodeling. Cell Rep. 2017;21:246–58.

Antonny B, Vanni S, Shindou H, Ferreira T. From zero to six double bonds: phospholipid unsaturation and organelle function. Trends Cell Biol. 2015;25:427–36.

Gawrisch K, Eldho NV, Holte LL. The structure of DHA in phospholipid membranes. Lipids. 2003;38:445–52.

Jacobs ML, Faizi HA, Peruzzi JA, Vlahovska PM, Kamat NP. EPA and DHA differentially modulate membrane elasticity in the presence of cholesterol. Biophys J. 2021;120:2317–29.

Alves I, Staneva G, Tessier C, Salgado GF, Nuss P. The interaction of antipsychotic drugs with lipids and subsequent lipid reorganization investigated using biophysical methods. Biochim Biophys Acta Biomembr 2011;1808:2009–18.

Tessier C, Nuss P, Staneva G, Wolf C. Modification of membrane heterogeneity by antipsychotic drugs: an X-ray diffraction comparative study. J Colloid Interface Sci. 2008;320:469–75.

Lolicato F, Juhola H, Zak A, Postila PA, Saukko A, Rissanen S, et al. Membrane-dependent binding and entry mechanism of dopamine into its receptor. ACS Chem Neurosci. 2020;11:1914–24.

Lemel L, Nieścierowicz K, García-Fernández MD, Darré L, Durroux T, Busnelli M, et al. The ligand-bound state of a G protein-coupled receptor stabilizes the interaction of functional cholesterol molecules. J Lipid Res. 2021;62:1–17.

Malnoe A, Milon H, Reme C. Effect of in vivo modulation of membrane docosahexaenoic acid levels on the dopamine‐dependent adenylate cyclase activity in the rat retina. J Neurochem. 1990;55:1480–5.

Murphy MG. Effects of exogenous linoleic acid on fatty acid composition, receptor-mediated cAMP formation, and transport functions in rat astrocytes in primary culture. Neurochem Res. 1995;20:1365–75.

Yu JZ, Wang J, Sheridan SD, Perlis RH, Rasenick MM. N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells. Mol Psychiatry. 2021;26:4605–15.

Latorraca NR, Venkatakrishnan AJ, Dror RO. GPCR dynamics: structures in motion. Chem Rev. 2017;117:139–55.

Weis WI, Kobilka BK. The molecular basis of G protein-coupled receptor activation. Annu Rev Biochem. 2018;87:897–919.

Chapkin RS, Wang N, Fan YY, Lupton JR, Prior IA. Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta - Biomembr. 2008;1778:466–71.

Levental KR, Lorent JH, Lin X, Skinkle AD, Surma MA, Stockenbojer EA, et al. Polyunsaturated lipids regulate membrane domain stability by tuning membrane order. Biophys J. 2016;110:1800–10.

Stillwell W, Shaikh SR, Zerouga M, Siddiqui R, Wassal SR. Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev. 2005;45:559–79.

Charest PG, Bouvier M. Palmitoylation of the V2 vasopressin receptor carboxyl tail enhances β-arrestin recruitment leading to efficient receptor endocytosis and ERK1/ 2 activation. J Biol Chem. 2003;278:41541–51.

Hawtin SR, Tobin AB, Patel S, Wheatley M. Palmitoylation of the vasopressin V1a receptor reveals different conformational requirements for signaling, agonist-induced receptor phosphorylation, and sequestration. J Biol Chem. 2001;276:38139–46.

Karnik SS, Ridge KD, Bhattacharya S, Khorana HG. Palmitoylation of bovine opsin and its cysteine mutants in COS cells. Proc Natl Acad Sci USA. 1993;90:40–44.

Moffett S, Mouillac B, Bonin H, Bouvier M. Altered phosphorylation and desensitization patterns of a human β2-adrenergic receptor lacking the palmitoylated Cys341. EMBO J. 1993;12:349–6.

Palmer TM, Stiles GL. Identification of threonine residues controlling the agonist- dependent phosphorylation and desensitization of the rat A3 adenosine receptor. Mol Pharm. 2000;57:539–45.

Pickering DS, Tavern FA, Salter MW, Hampson DR.Palmitoylation of the GluR6 kainate receptor.Proc Natl Acad Sci USA.1995;92:12090–4.

Lally CCM, Bauer B, Selent J, Sommer ME. C-edge loops of arrestin function as a membrane anchor. Nat Commun. 2017;8:1–12.

Cho D, Zheng M, Min C, Ma L, Kurose H, Park JH, et al. Agonist-induced endocytosis and receptor phosphorylation mediate resensitization of dopamine D2 receptors. Mol Endocrinol. 2010;24:574–86.

Lan H, Teeter MM, Gurevich VV, Neve KA. An intracellular loop 2 amino acid residue determines differential binding of arrestin to the dopamine D 2 and D 3 receptors. Mol Pharm. 2009;75:19–26.

Zhang X, Choi BG, Kim KM. Roles of dopamine D2 receptor subregions in interactions with β-arrestin2. Biomol Ther. 2016;24:517–22.

Donthamsetti P, Gallo EF, Buck DC, Stahl EL, Zhu Y, Lane JR, et al. Arrestin recruitment to dopamine D2 receptor mediates locomotion but not incentive motivation. Mol Psychiatry. 2020;25:2086–2100.

Rooster EF, Meszaros J, Sherman JD, Chohan MO, Teboul E, Choi CS, et al.Accumbens dopamine D2 receptors increase motivation by decreasing inhibitory transmission to the ventral pallidum.Nat Commun.2018;9:1–1

Berger GE, Proffitt T-M, McConchie M, Yuen H, Wood SJ, Amminger GP, et al. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J Clin Psychiatry. 2007;68:1867–75.

Robinson DG, Gallego JA, John M, Hanna LA, Zhang JP, Birnbaum ML, et al. A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone. Schizophr Res. 2019;204:295–303.

Amminger GP, Schäfer MR, Schlögelhofer M, Klier CM, McGorry PD. Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study. Nat Commun. 2015;6:1–7.

Rodríguez-Espigares I, Torrens-Fontanals M, Tiemann JKS, Aranda-García D, Ramírez-Anguita JM, Stepniewski TM, et al.GPCRmd uncovers the dynamics of the 3D-GPCRome.Nat Methods.2020;17:777–87.

We thank the biochemistry facility of the Bordeaux Neurocampus for the access to the blot imaging system, JJ. Toulmé for use of the fluorescence spectrometer (TECAN), JL. Banères for providing D2R expressing Pichia pastoris and the Bordeaux Metabolome Facility-MetaboHUB (ANR-11-INBS-0010). This study was supported by INRAE, CNRS and the University of Bordeaux; University of Bordeaux’s IdEx “Investments for the future” program/GPR BRAIN_203 (PT), Idex Bordeaux “chaire d’installation” (ANR-10-IDEX-03-02) (PT), NARSAD Young Investigator Grants from the Brain and Behavior Foundation (PT), ANR “SynLip” (ANR-16-CE16-0022) (PT), ANR “FrontoFat” (ANR-20-CE14-0020) (PT), ANR “PolyFADO” (ANR-21-CE44-0019-02) (IA and PT), Region Nouvelle Aquitaine 2014-1R30301-00003023 (PT), Région Nouvelle Aquitaine (2011 13 04 002) (IA), PEPS Emergence Idex Bordeaux (2012) (IA), NIH grant MH54137 (JAJ), the Instituto de Salud Carlos III FEDER (PI18/00094) and the ERA-NET NEURON & Ministry of Economy, Industry and Competitiveness (AC18/00030) (JS), the European Research Network on Signal Transduction ( (COST Action CA18133) (BM, RG-G, JS), the Swiss National Science Foundation, grant no. 192780 (RG-G).

These authors contributed equally: Marie-Lise Jobin, Véronique De Smedt-Peyrusse.

These authors jointly supervised this work: Ramon Guixà-González, Isabel D. Alves, Pierre Trifilieff.

University of Bordeaux, INRAE, Bordeaux INP, NutriNeuro, 33000, Bordeaux, France

Marie-Lise Jobin, Véronique De Smedt-Peyrusse, Fabien Ducrocq, Asma Oummadi, Maria-Florencia Angelo & Pierre Trifilieff

Institute of Chemistry & Biology of Membranes & Nanoobjects, CNRS UMR 5248, Université de Bordeaux, Bordeaux INP, 33600, Pessac, France

Rim Baccouch, Sandrine Villette & Isabel D. Alves

Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

Maria Hauge Pedersen & Jonathan A. Javitch

Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, 10032, USA

Maria Hauge Pedersen & Jonathan A. Javitch

Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM)—Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), 08003, Barcelona, Spain

Brian Medel-Lacruz & Jana Selent

Laboratory of Membrane Biogenesis (LBM), Research Mix Unity (UMR) 5200, National Scientific Research Center (CNRS), University of Bordeaux, Bordeaux, France

Pierre Van Delft, Laetitia Fouillen & Sébastien Mongrand

Research Department, IMG Pharma Biotech S.L., BIC Bizkaia (612), 48160, Derio, Spain

Tarson Tolentino-Cortez & Gabriel Barreda-Gomez

Taste and Food Science Center, AgroSup Dijon, CNRS, INRAE, Bourgogne Franche-Comté University, 21000, Dijon, France

Stéphane Grégoire & Elodie Masson

Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, Montpellier, France

Department of Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

Condensed Matter Theory Group, Paul Scherrer Institute (PSI), 5232, Villigen, PSI, Switzerland

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

You can also search for this author in PubMed  Google Scholar

M-LJ, VDP, RG-G, IDA and PT conceived and supervised the study. JS, GB-G, EM, TD and JAJ provided expertise, reagents and supervised specific experiments. M-LJ, VDP, FD, AO, RB, M-FA, MHP, BM-L, JS, SM, SV, TT-C, SG and RG-G performed experiments and analyzed the data. M-LJ, VDP, RG-G, IDA and PT wrote the original version of the manuscript. All authors discussed the results and reviewed the manuscript.

Correspondence to Ramon Guixà-González, Isabel D. Alves or Pierre Trifilieff.

The authors declare no competing interests.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Jobin, ML., De Smedt-Peyrusse, V., Ducrocq, F. et al. Impact of membrane lipid polyunsaturation on dopamine D2 receptor ligand binding and signaling. Mol Psychiatry (2023).


Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

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

Humic Acid Fertilizer Molecular Psychiatry (Mol Psychiatry) ISSN 1476-5578 (online) ISSN 1359-4184 (print)