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Identification of BiP as a CB1 receptor-interacting protein that fine-tunes cannabinoid signaling in the mouse brain

dc.rights.licenseopenen_US
dc.contributor.authorCOSTAS-INSUA, Carlos
dc.contributor.authorMORENO, Estefania
dc.contributor.authorMAROTO, Irene B.
dc.contributor.authorRUIZ-CALVO, Andrea
dc.contributor.authorBAJO-GRANERAS, Raquel
dc.contributor.authorMARTIN-GUTIERREZ, David
dc.contributor.authorDIEZ-ALARCIA, Rebeca
dc.contributor.authorVILARO, Teresa M.
dc.contributor.authorCORTES, Roser
dc.contributor.authorGARCIA-FONT, Nuria
dc.contributor.authorMARTIN, Ricardo
dc.contributor.authorESPINA, Marc
dc.contributor.authorBOTTA, Joaquin
dc.contributor.authorGINES, Silvia
dc.contributor.authorMCCORMICK, Peter J.
dc.contributor.authorSANCHEZ-PRIETO, Jose
dc.contributor.authorGALVE-ROPERH, Ismael
dc.contributor.authorMENGOD, Guadalupe
dc.contributor.authorURIGUEN, Leyre
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMARSICANO, Giovanni
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBELLOCCHIO, Luigi
dc.contributor.authorCANELA, Enrice I.
dc.contributor.authorCASADO, Vicent
dc.contributor.authorRODRIGUEZ-CRESPO, Ignacio
dc.contributor.authorGUZMAN, Manuel
dc.date.accessioned2021-11-22T08:00:49Z
dc.date.available2021-11-22T08:00:49Z
dc.date.issued2021-09-22
dc.identifier.issn1529-2401en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/123884
dc.description.abstractEnCannabinoids, the bioactive constituents of cannabis, exert a wide array of effects on the brain by engaging Type 1 cannabinoid receptor (CB1R). Accruing evidence supports that cannabinoid action relies on context-dependent factors, such as the biological characteristics of the target cell, suggesting that cell population-intrinsic molecular cues modulate CB1R-dependent signaling. Here, by using a yeast two-hybrid-based high-throughput screening, we identified BiP as a potential CB1R-interacting protein. We next found that CB1R and BiP interact specifically in vitro, and mapped the interaction site within the CB1R C-terminal (intracellular) domain and the BiP C-terminal (substrate-binding) domain-a. BiP selectively shaped agonist-evoked CB1R signaling by blocking an "alternative" Gq/11 protein-dependent signaling module while leaving the "classical" Gi/o protein-dependent inhibition of the cAMP pathway unaffected. In situ proximity ligation assays conducted on brain samples from various genetic mouse models of conditional loss or gain of CB1R expression allowed to map CB1R-BiP complexes selectively on terminals of GABAergic neurons. Behavioral studies using cannabinoid- treated male BiP1/2 mice supported that CB1R-BiP complexes modulate cannabinoid-evoked anxiety, one of the most frequent undesired effects of cannabis. Together, by identifying BiP as a CB1R-interacting protein that controls receptor function in a signaling pathway- and neuron population-selective manner, our findings may help to understand the striking context-dependent actions of cannabis in the brain.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enBiP
dc.subject.enCannabinoid
dc.subject.enCell signaling
dc.subject.enG-protein-coupled receptor
dc.subject.enNeurotransmission
dc.subject.enProtein-protein interaction
dc.titleIdentification of BiP as a CB1 receptor-interacting protein that fine-tunes cannabinoid signaling in the mouse brain
dc.title.alternativeJ Neurosci.en_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1523/JNEUROSCI.0821-21.2021en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed34353897en_US
bordeaux.journalJournal of Neuroscienceen_US
bordeaux.page7924-7941en_US
bordeaux.volume41en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - UMR-S 1215en_US
bordeaux.issue38en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDInstitut National de la Santé et de la Recherche Médicaleen_US
bordeaux.identifier.funderIDCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativasen_US
bordeaux.identifier.funderIDBiotechnology and Biological Sciences Research Councilen_US
bordeaux.identifier.funderIDMinisterio de Ciencia, Innovación y Universidadesen_US
hal.identifierhal-03438884
hal.version1
hal.date.transferred2021-11-22T08:00:56Z
hal.exporttrue
dc.rights.ccCC BYen_US
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