論文 - 詳細
| RRC ID | 35984 |
|---|---|
| 著者 | Moreno JL, Miranda-Azpiazu P, García-Bea A, Younkin J, Cui M, Kozlenkov A, Ben-Ezra A, Voloudakis G, Fakira AK, Baki L, Ge Y, Georgakopoulos A, Morón JA, Milligan G, López-Giménez JF, Robakis NK, Logothetis DE, Meana JJ, González-Maeso J. |
| タイトル | Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. |
| ジャーナル | Sci Signal |
| Abstract |
Heterotrimeric 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 Gq/11-coupled serotonin 5-HT2A receptor and the Gi/o-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-HT2A heteromers with an mGlu2 agonist led to activation of Gq/11 proteins by the 5-HT2A receptors. For this crosstalk to occur, one of the mGlu2 subunits had to couple to Gi/o proteins, and we determined the relative location of the Gi/o-contacting subunit within the mGlu2 homodimer of the heteromeric complex. Additionally, mGlu2-dependent activation of Gq/11, but not Gi/o, was reduced in the frontal cortex of 5-HT2A 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. |
| 巻・号 | 9(410) |
| ページ | ra5 |
| 公開日 | 2016-1-12 |
| DOI | 10.1126/scisignal.aab0467 |
| PII | 9/410/ra5 |
| PMID | 26758213 |
| PMC | PMC4819166 |
| MeSH | Allosteric Regulation Animals GTP-Binding Protein alpha Subunits, Gi-Go / genetics GTP-Binding Protein alpha Subunits, Gi-Go / metabolism GTP-Binding Protein alpha Subunits, Gq-G11 / genetics GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism HEK293 Cells Humans Mice Mice, Knockout Protein Multimerization* Receptor, Serotonin, 5-HT2A / genetics Receptor, Serotonin, 5-HT2A / metabolism* Receptors, Metabotropic Glutamate / genetics Receptors, Metabotropic Glutamate / metabolism* Schizophrenia / genetics Schizophrenia / metabolism* Signal Transduction* |
| IF | 6.467 |
| 引用数 | 44 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01351 |