ArticleCell reports2020
An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIα Phosphorylation of GluN2A and NMDA Receptor Trafficking.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- Serum MAP1A as a Potential Biomarker for Autism Spectrum Disorder.Brain sciences · 2026Article
- Neto2 Phosphorylation Promotes Neuronal Loss in KA-Induced Epileptic Rat Hippocampus by Upregulating the Interaction with GluK2.Neurochemical research · 2026Article
- Increased NMDAR activity and GluN2A-NMDAR silent synapse expansion induced by chronic benzodiazepine treatment.Neuropharmacology · 2025Article
- [Landau-Kleffner Syndrome: Current Etiopathogenesis and Management].Revista de neurologia · 2025Review
- Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications.Neurochemical research · 2025Review
- Functional ultrasound imaging and prewhitening analysis reveal MK-801-induced disruption of brain network connectivity.Frontiers in pharmacology · 2025Article
- Clinical phenotype and functional influence of GRIN2A variants in epilepsy-aphasia syndrome.Epilepsia open · 2024Article
- Classification of Current Experimental Models of Epilepsy.Brain sciences · 2024Review
- Myosin Va-dependent Transport of NMDA Receptors in Hippocampal Neurons.Neuroscience bulletin · 2024Article
- Individual NMDA receptor GluN2 subunit signaling domains differentially regulate the postnatal maturation of hippocampal excitatory synaptic transmission and plasticity but not dendritic morphology.Synapse (New York, N.Y.) · 2024Article
- Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology.Physiological research · 2024Review
- A Frameshift Variant of GluN2A Identified in an Epilepsy Patient Results in NMDA Receptor Mistargeting.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.Cellular and molecular life sciences : CMLS · 2024Article
- Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes.Nature reviews. Neurology · 2024Review
- Analysis of Surface Expression of NMDAR Subunits in Primary Hippocampal Neurons.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Classification of missense variants in the N-methyl-d-aspartate receptor GRIN gene family as gain- or loss-of-function.Human molecular genetics · 2023Article
- In the fast lane: Receptor trafficking during status epilepticus.Epilepsia open · 2023Review
- Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.International journal of molecular sciences · 2023Review
- Systematic Assessment of Protein C-Termini Mutated in Human Disorders.Biomolecules · 2023Article
- Progresses in GluN2A-containing NMDA Receptors and their Selective Regulators.Cellular and molecular neurobiology · 2023Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Rare variants in GRIN genes, which encode NMDAR subunits, are strongly associated with neurodevelopmental disorders. Among these, GRIN2A, which encodes the GluN2A subunit of NMDARs, is widely accepted as an epilepsy-causative gene. Here, we functionally characterize the de novo GluN2A-S1459G mutation identified in an epilepsy patient. We show that S1459 is a CaMKIIα phosphorylation site, and that endogenous phosphorylation is regulated during development and in response to synaptic activity in a dark rearing model. GluN2A-S1459 phosphorylation results in preferential binding of NMDARs to SNX27 and a corresponding decrease in PSD-95 binding, which consequently regulates NMDAR trafficking. Furthermore, the epilepsy-associated GluN2A-S1459G variant displays defects in interactions with both SNX27 and PSD-95, resulting in trafficking deficits, reduced spine density, and decreased excitatory synaptic transmission. These data demonstrate a role for CaMKIIα phosphorylation of GluN2A in receptor targeting and implicate NMDAR trafficking defects as a link to epilepsy.
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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 Socratic graph.