Miniatura

Fitxers

713779.pdf (5.22 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2021-08-05

Llicència de publicació

cc-by-nc-sa (c) Costas-Insua, Carlos et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/181159

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

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1523/JNEUROSCI.0821-21.2021

Resum

Cannabinoids, 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-α. 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 BiP+/- mice supported that CB1R-BiP complexes modulate cannabinoid-evoked anxiety, one of the most frequent undesired effects of cannabis. Altogether, 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.

Matèries

Neurotransmissió, Cànnabis, Proteïnes

Matèries (anglès)

Neural transmission, Cannabis, Proteins

Citació

Col·leccions

Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

Citació

COSTAS-INSUA, Carlos, MORENO GUILLÉN, Estefanía, MAROTO, Irene b., RUIZ-CALVO, Andrea, BAJO-GRAÑERAS, Raquel, MARTÍN-GUTIÉRREZ, David, DIEZ-ALARCIA, Rebeca, VILARÓ, M.teresa, CORTÉS, Roser, GARCÍA-FONT, Nuria, MARTÍN, Ricardo, ESPINA, Marc, BOTTA, Joaquín, GINÉS PADRÓS, Silvia, MCCORMICK, Peter j., SÁNCHEZ-PRIETO, José, GALVE-ROPERH, Ismael, MENGOD, Guadalupe, URIGÜEN, Leyre, MARSICANO, Giovanni, BELLOCCHIO, Luigi, CANELA CAMPOS, Enric i. (enric isidre), CASADÓ, Vicent, RODRÍGUEZ-CRESPO, Ignacio, GUZMÁN, Manuel. Identification of BiP as a CB1 receptor-interacting protein that fine-tunes cannabinoid signaling in the mouse brain. _Journal of Neuroscience_. 2021. Vol. 41, núm. 38, pàgs. 7924-7941. [consulta: 24 de gener de 2026]. ISSN: 0270-6474. [Disponible a: https://hdl.handle.net/2445/181159]

Exportar metadades

JSON - METS

Compartir registre