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Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia

AutorMoreno, José L.; López-Giménez, Juan F. ; Meana, J. J.; González-Maeso, Javier
Fecha de publicación2016
EditorAmerican Association for the Advancement of Science
CitaciónScience signaling 9(410): ra5 (2016)
ResumenHeterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) can form multiprotein complexes (heteromers), which can alter the pharmacology and functions of the constituent receptors. Previous findings demonstrated that the G-coupled serotonin 5-HTA receptor and the G-coupled metabotropic glutamate 2 (mGlu2) receptor-GPCRs that are involved in signaling alterations associated with psychosis-assemble into a heteromeric complex in the mammalian brain. In single-cell experiments with various mutant versions of the mGlu2 receptor, we showed that stimulation of cells expressing mGlu2-5-HT heteromers with an mGlu2 agonist led to activation of G proteins by the 5-HTA receptors. For this crosstalk to occur, one of the mGlu2 subunits had to couple to G proteins, and we determined the relative location of the G-contacting subunit within the mGlu2 homodimer of the heteromeric complex. Additionally, mGlu2-dependent activation of G, but not G, was reduced in the frontal cortex of 5-HT knockout mice and was reduced in the frontal cortex of postmortem brains from schizophrenic patients. These findings offer structural insights into this important target in molecular psychiatry.
DescripciónPMCID: PMC4819166.-- Moreno et al.
Versión del editorhttps://doi.org/10.1126/scisignal.aab0467
URIhttp://hdl.handle.net/10261/164275
Identificadoresdoi: 10.1126/scisignal.aab0467
e-issn: 1937-9145
issn: 1945-0877
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