ArticleProceedings of the National Academy of Sciences of the United States of America2012
Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 169 citations in OpenAlex.
- Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HTNature communications · 2026Article
- Both calcium-sensing receptor intracellular C-terminal domains support homodimer signaling.Molecular pharmacology · 2025Article
- Metabotropic glutamate receptor homo- and heterodimers exhibit distinct responses to orthosteric and allosteric ligands.Molecular pharmacology · 2025Article
- Disruption of constitutive CXCR4 oligomers impairs oncogenic properties in lymphoid neoplasms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inosine-5'-monophosphate interacts with the TAS1R3 subunit to enhance sweet taste detection.Food chemistry. Molecular sciences · 2025Article
- Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.Nature communications · 2024Article
- Nanodisc Technology: Direction toward Physicochemical Characterization of Chemosensory Membrane Proteins in Food Flavor Research.Journal of agricultural and food chemistry · 2024Review
- Article
- The Role of G Protein-Coupled Receptors and Receptor Kinases in PancreaticPharmacological reviews · 2024Review
- Decrypting orphan GPCR drug discovery via multitask learning.Journal of cheminformatics · 2024Article
- Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers.Science advances · 2023Article
- mGluR5 from Primary Sensory Neurons Promotes Opioid-Induced Hyperalgesia and Tolerance by Interacting with and Potentiating Synaptic NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- GRM7 gene mutations and consequences for neurodevelopment.Pharmacology, biochemistry, and behavior · 2023Review
- Multiple mechanisms of self-association of chemokine receptors CXCR4 and CCR5 demonstrated by deep mutagenesis.bioRxiv : the preprint server for biology · 2023Article
- Kinetic fingerprinting of metabotropic glutamate receptors.Communications biology · 2023Article
- Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects CaJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Nanobody-based sensors reveal a high proportion of mGlu heterodimers in the brain.Nature chemical biology · 2022Article
- Class A and C GPCR Dimers in Neurodegenerative Diseases.Current neuropharmacology · 2022Review
- Reduced Metabotropic Glutamate Receptor Type 5 Availability in the Epileptogenic Hippocampus: AnFrontiers in neurology · 2022Article
- Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line.Scientific reports · 2021Article
26 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
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eight metabotropic glutamate receptors (mGluRs) are key modulators of synaptic transmission and are considered promising targets for the treatment of various brain disorders. Whereas glutamate acts at a large extracellular domain, allosteric modulators have been identified that bind to the seven transmembrane domain (7TM) of these dimeric G-protein-coupled receptors (GPCRs). We show here that the dimeric organization of mGluRs is required for the modulation of active and inactive states of the 7TM by agonists, but is not necessary for G-protein activation. Monomeric mGlu2, either as an isolated 7TM or in full-length, purified and reconstituted into nanodiscs, couples to G proteins upon direct activation by a positive allosteric modulator. However, only a reconstituted full-length dimeric mGlu2 activates G protein upon glutamate binding, suggesting that dimerization is required for glutamate induced activation. These data show that, even for such well characterized GPCR dimers like mGluR2, a single 7TM is sufficient for G-protein coupling. Despite this observation, the necessity of dimeric architecture for signaling induced by the endogenous ligand glutamate confirms that the central core of signaling complex is dimeric.
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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.