ArticleThe Journal of biological chemistry2013
Agonist-dependent signaling by group I metabotropic glutamate receptors is regulated by association with lipid domains.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- Spinocerebellar Ataxia 44 Caused by a Novel GRM1 Variant: Reviewing the Contrasting Pathogenic Mechanisms Underlying Two GRM1-Associated Hereditary Ataxias.Cerebellum (London, England) · 2025Article
- Evolutionary history of calcium-sensing receptors unveils hyper/hypocalcemia-causing mutations.PLoS computational biology · 2024Article
- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Molecules (Basel, Switzerland) · 2023Review
- Cholesterol in Class C GPCRs: Role, Relevance, and Localization.Membranes · 2023Article
- Cyclodextrins: Only Pharmaceutical Excipients or Full-Fledged Drug Candidates?Pharmaceutics · 2022Review
- Group I mGluRs in Therapy and Diagnosis of Parkinson's Disease: Focus on mGluR5 Subtype.Biomedicines · 2022Review
- Structural determinants of cholesterol recognition in helical integral membrane proteins.Biophysical journal · 2021Article
- Metabotropic Glutamate Receptor Trafficking and its Role in Drug-Induced Neurobehavioral Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2021Review
- Contribution of Membrane Lipids to Postsynaptic Protein Organization.Frontiers in synaptic neuroscience · 2021Review
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- Statins and the Brain: More than Lipid Lowering Agents?Current neuropharmacology · 2019Review
- The actions of volatile anesthetics: a new perspective.Acta crystallographica. Section D, Structural biology · 2018Review
- Functional organization of postsynaptic glutamate receptors.Molecular and cellular neurosciences · 2018Review
- Metabotropic glutamate receptor trafficking.Molecular and cellular neurosciences · 2018Review
- Group I Metabotropic Glutamate Receptor Interacting Proteins: Fine-Tuning Receptor Functions in Health and Disease.Current neuropharmacology · 2016Review
- Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes.Frontiers in cellular neuroscience · 2015Review
- Quantitative profiling of brain lipid raft proteome in a mouse model of fragile X syndrome.PloS one · 2015Article
- Lipid rafts in neurodegeneration and neuroprotection.Molecular neurobiology · 2014Review
- Lipid rafts serve as signaling platforms for mGlu1 receptor-mediated calcium signaling in association with caveolin.Molecular brain · 2014Article
- Lipid rafts: a signaling platform linking cholesterol metabolism to synaptic deficits in autism spectrum disorders.Frontiers in behavioral neuroscience · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, play critical functions in forms of activity-dependent synaptic plasticity and synapse remodeling in physiological and pathological states. Importantly, in animal models of fragile X syndrome, group I mGluR activity is abnormally enhanced, a dysfunction that may partly underlie cognitive deficits in the condition. Lipid rafts are cholesterol- and sphingolipid-enriched membrane domains that are thought to form transient signaling platforms for ligand-activated receptors. Many G protein-coupled receptors, including group I mGluRs, are present in lipid rafts, but the mechanisms underlying recruitment to these membrane domains remain incompletely understood. Here, we show that mGluR1 recruitment to lipid rafts is enhanced by agonist binding and is supported at least in part by an intact cholesterol recognition/interaction amino acid consensus (CRAC) motif in the receptor. Substitutions of critical residues in the motif reduce mGluR1 association with lipid rafts and agonist-induced, mGluR1-dependent activation of extracellular-signal-activated kinase1/2 MAP kinase (ERK-MAPK). We find that alteration of membrane cholesterol content or perturbation of lipid rafts regulates agonist-dependent activation of ERK-MAPK by group I mGluRs, suggesting a potential function for cholesterol as a positive allosteric modulator of receptor function(s). Together, these findings suggest that drugs that alter membrane cholesterol levels or directed to the receptor-cholesterol interface could be employed to modulate abnormal group I mGluR activity in neuropsychiatric conditions, including fragile X syndrome.
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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.