Evidence against dopamine D1/D2 receptor heteromers
| dc.rights.license | open | en_US |
| dc.contributor.author | FREDERICK, A. L. | |
| dc.contributor.author | YANO, H. | |
| hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
| dc.contributor.author | TRIFILIEFF, Pierre | |
| dc.contributor.author | VISHWASRAO, H. D. | |
| dc.contributor.author | BIEZONSKI, Dominik K. | |
| dc.contributor.author | MESZAROS, Jozsef | |
| dc.contributor.author | URIZAR, E. | |
| dc.contributor.author | SIBLEY, David R. | |
| dc.contributor.author | KELLENDONK, Christoph | |
| dc.contributor.author | SONNTAG, K. C. | |
| dc.contributor.author | GRAHAM, Danielle | |
| dc.contributor.author | COLBRAN, R. J. | |
| dc.contributor.author | STANWOOD, G. D. | |
| dc.contributor.author | JAVITCH, Jonathan A. | |
| dc.date.accessioned | 2021-09-06T14:43:31Z | |
| dc.date.available | 2021-09-06T14:43:31Z | |
| dc.date.issued | 2015-11 | |
| dc.identifier.issn | 1476-5578 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/112113 | |
| dc.description.abstractEn | Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout (KO) mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq KO mice, as well as in knock-in mice expressing a mutant Ala(286)-CaMKIIα that cannot autophosphorylate to become active. Moreover, we found that, in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1/D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | Animals | |
| dc.subject.en | Corpus Striatum | |
| dc.subject.en | Dopamine Agonists | |
| dc.subject.en | Dopamine Antagonists | |
| dc.subject.en | Grooming | |
| dc.subject.en | GTP-Binding Protein alpha Subunits | |
| dc.subject.en | Gq-G11 | |
| dc.subject.en | HEK293 Cells | |
| dc.subject.en | Humans | |
| dc.subject.en | Luminescent Proteins | |
| dc.subject.en | Male | |
| dc.subject.en | Mice | |
| dc.subject.en | Inbred C57BL | |
| dc.subject.en | Knockout | |
| dc.subject.en | Models | |
| dc.subject.en | Molecular | |
| dc.subject.en | Motor Activity | |
| dc.subject.en | Nucleus Accumbens | |
| dc.subject.en | Phosphorylation | |
| dc.subject.en | Protein Multimerization | |
| dc.subject.en | Protein Structure | |
| dc.subject.en | Tertiary | |
| dc.subject.en | Receptors Dopamine D1 | |
| dc.subject.en | Receptors Dopamine D2 | |
| dc.title.en | Evidence against dopamine D1/D2 receptor heteromers | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/mp.2014.166 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC] | en_US |
| dc.identifier.pubmed | 25560761 | en_US |
| bordeaux.journal | Molecular Psychiatry | en_US |
| bordeaux.page | 1373-1385 | en_US |
| bordeaux.volume | 20 | en_US |
| bordeaux.hal.laboratories | NutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286 | en_US |
| bordeaux.issue | 11 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INRAE | en_US |
| bordeaux.team | Psychoneuroimmunologie et Nutrition: Approches expérimentales et cliniques | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.identifier.funderID | Institut National de la Santé et de la Recherche Médicale | en_US |
| hal.export | false | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Psychiatry&rft.date=2015-11&rft.volume=20&rft.issue=11&rft.spage=1373-1385&rft.epage=1373-1385&rft.eissn=1476-5578&rft.issn=1476-5578&rft.au=FREDERICK,%20A.%20L.&YANO,%20H.&TRIFILIEFF,%20Pierre&VISHWASRAO,%20H.%20D.&BIEZONSKI,%20Dominik%20K.&rft.genre=article |
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