ArticleScience signaling2016
Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 111 citations in OpenAlex.
- GPCR heteromers: Beyond the monomeric paradigm in neuropsychiatric drug discovery.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- No evidence for direct physical interaction of 5-HTbioRxiv : the preprint server for biology · 2026Article
- Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.Translational psychiatry · 2026Review
- Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HTNature communications · 2026Article
- Glutamate Metabotropic Receptors-Linked Postsynaptic Density Proteins: An Emergent Hub for Antipsychotics' Regulation of Synaptic Plasticity and Metaplasticity.Biomolecules · 2026Review
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Above the threshold, beyond the trip: the role of the 5-HTMolecular psychiatry · 2025Review
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Serotonin 5-HT2A receptor expression is chronically decreased in the anterior cerebral cortex of male rats following repetitive low-level blast exposure.Frontiers in neurology · 2025Article
- Epigenetic mechanisms of rapid-acting antidepressants.Translational psychiatry · 2024Review
- Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HTMolecular psychiatry · 2024Article
- Article
- The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review.Molecules (Basel, Switzerland) · 2024Review
- Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis.Nature communications · 2024Article
- Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review).International journal of molecular medicine · 2024Review
- Visual mismatch negativity in Parkinson's psychosis and potential for testing treatment mechanisms.Brain communications · 2024Article
- Psychedelics action and schizophrenia.Pharmacological reports : PR · 2023Review
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics.Biology · 2023Review
- Mechanisms and molecular targets surrounding the potential therapeutic effects of psychedelics.Molecular psychiatry · 2023Review
- The crosstalk between 5-HTNeuropharmacology · 2023Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.