Affinage

GRIN2A

Glutamate receptor ionotropic, NMDA 2A · UniProt Q12879

Length
1464 aa
Mass
165.3 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIN2A encodes the GluN2A subunit of the NMDA receptor, which co-assembles with GluN1 to form the predominant synaptic NMDA receptor in the adult forebrain, conferring fast deactivation kinetics, high open probability, nanomolar zinc sensitivity, and voltage-dependent Mg²⁺ block that are essential for synaptic plasticity and circuit maturation (PMID:7904155, PMID:15649985, PMID:30500536, PMID:9065507). The GluN2A amino-terminal domain mediates high-affinity zinc inhibition through an allosteric pathway that constricts the ion channel gate, while the cytoplasmic C-terminal tail suppresses LTP induction and undergoes CaMKIIα phosphorylation at Ser-1459 to promote SNX27-retromer-dependent endosomal recycling and Src-family-kinase phosphorylation at Tyr-1325 to sustain channel activity via a Pyk2–Src feed-forward loop coupled to ERK MAPK signaling (PMID:30500536, PMID:21725314, PMID:20164351, PMID:34186182, PMID:19834457, PMID:38569938). Dendritic GluN2A mRNA undergoes CPE-dependent local translation to supply activity-induced receptor insertion, while an ER-retention KKK motif and KIF3B-mediated vesicular transport regulate forward trafficking (PMID:23678131, PMID:35484243, PMID:31746486). Disease-causing GRIN2A variants in transmembrane/linker domains produce gain-of-function (epileptic encephalopathy with seizures), whereas agonist-binding domain, amino-terminal domain, and null variants cause loss-of-function, with clinical severity—ranging from epilepsy-aphasia spectrum to severe developmental delay—predictable from the direction and magnitude of NMDAR functional change (PMID:30544257, PMID:32577763, PMID:38307912).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 1993 High

    Establishing that NR2A co-assembles with NR1 to reconstitute a functional heteromeric NMDA receptor answered the fundamental question of subunit stoichiometry and provided the basis for all subsequent subunit-specific studies.

    Evidence Co-expression in HEK293 cells with [³H]MK801 binding showing 10-fold increase over single subunits

    PMID:7904155

    Open questions at the time
    • Native stoichiometry (2 GluN1 + 2 GluN2A) not yet determined
    • Triheteromeric assemblies not addressed
  2. 1997 High

    Demonstrating that NR2A expression directly shortens NMDAR synaptic current duration in developing neocortex established GluN2A as the molecular switch for the developmental speeding of NMDAR kinetics.

    Evidence Single-cell RT-PCR combined with patch-clamp in postnatal rat cortical neurons

    PMID:9065507

    Open questions at the time
    • Whether NR2A is sufficient or merely correlated at the circuit level
    • Contribution of triheteromeric NR2A/NR2B receptors not resolved
  3. 2003 High

    Identifying SAP97 as a direct PDZ1-domain partner of NR2A whose interaction is disrupted by CaMKII phosphorylation at SAP97-Ser232 revealed the first regulated scaffolding mechanism for synaptic NR2A targeting.

    Evidence Reciprocal co-IP from hippocampal synaptosomes, pull-down, and phosphomimetic mutagenesis (S232D) in COS-7 cells

    PMID:12933808

    Open questions at the time
    • In vivo contribution of SAP97-S232 phosphorylation to NR2A synaptic content not tested
    • Relative importance vs. PSD-95 scaffolding unclear
  4. 2004 High

    Showing that PSD-95 differentially modulates NR2A channel function—increasing current yet blocking Src- and PKC-mediated potentiation—established PDZ proteins as bidirectional regulators of NR2A signaling.

    Evidence Reconstitution in Xenopus oocytes with PDZ domain chimeras and two-electrode voltage clamp

    PMID:15030393

    Open questions at the time
    • Which specific PDZ domain mediates each effect on NR2A in neurons not resolved
    • Endogenous stoichiometry of PDZ interactions at the synapse unknown
  5. 2005 High

    Quantifying NR2A-containing receptors' higher open probability (0.50 vs. 0.12 for NR2B) and faster pre-gating transitions resolved why the developmental NR2B-to-NR2A switch accelerates synaptic NMDAR signaling.

    Evidence Single-channel patch-clamp of recombinant NR1/NR2A vs. NR1/NR2B in HEK293 cells with kinetic modeling

    PMID:15649985

    Open questions at the time
    • Gating properties of native triheteromeric receptors not measured
    • Structural basis for faster conformational transitions unknown at the time
  6. 2006 High

    Live single-particle tracking revealed that NR2A-containing NMDARs are more stable at the neuronal surface than NR2B-containing ones, providing the biophysical basis for preferential NR2A synaptic accumulation during development.

    Evidence Single-molecule tracking with subunit-specific extracellular antibodies in cultured neurons

    PMID:17124177

    Open questions at the time
    • Molecular determinants of longer NR2A dwell time not identified
    • Whether stability difference holds at excitatory vs. extrasynaptic sites in vivo unclear
  7. 2009 High

    Knock-in mice with GluN2A-Y1325F established that Src-family-kinase phosphorylation at Tyr-1325 potentiates channel activity and feeds into DARPP-32 signaling in striatum, linking a specific NR2A phosphosite to downstream signaling and depression-related behavior.

    Evidence Y1325F knock-in mice; electrophysiology in striatal neurons; DARPP-32 biochemistry; behavioral tests

    PMID:19834457

    Open questions at the time
    • Identity of the phosphatase counteracting Y1325 phosphorylation in vivo not established
    • Whether Y1325 phosphorylation affects receptor trafficking in addition to gating unclear
  8. 2010 High

    Rescue experiments with C-terminal deletion constructs revealed that the GluN2A cytoplasmic tail actively suppresses LTP, fundamentally altering the view that subunit identity acts primarily through channel properties rather than intracellular scaffolding.

    Evidence RNAi knockdown/overexpression of WT, chimeric, and C-terminal deletion NR2A/NR2B in organotypic hippocampal slices with LTP recordings

    PMID:20164351

    Open questions at the time
    • Which C-terminal motifs or binding partners mediate LTP suppression not mapped
    • Whether the tail acts by recruiting inhibitory phosphatases or other effectors unknown
  9. 2010 High

    The GRIN2A p.N615K disease mutation demonstrated that a single pore residue controls both Mg²⁺ block and Ca²⁺ selectivity, providing the first direct link between a GRIN2A coding variant and altered channel biophysics in disease.

    Evidence Two-electrode voltage clamp of recombinant NR1-NR2A(N615K) receptors

    PMID:20890276

    Open questions at the time
    • In vivo neuronal consequences of N615K not tested at this stage
    • Whether loss of Mg²⁺ block or altered Ca²⁺ permeability is the primary pathogenic mechanism undetermined
  10. 2011 High

    NR2A-H128S knock-in mice proved that nanomolar zinc inhibition is mediated exclusively through the NR2A amino-terminal domain and has physiological relevance for pain processing in vivo.

    Evidence H128S knock-in mice; hippocampal and spinal cord slice electrophysiology; multiple pain behavioral models

    PMID:21725314

    Open questions at the time
    • Source of endogenous zinc acting on NR2A in spinal circuits not identified
    • Whether zinc modulation of NR2A contributes to other sensory modalities unknown
  11. 2011 High

    IQGAP1 was identified as a component of NR2A-NMDAR complexes that regulates surface NR2A levels and couples NR2A activation to ERK1/2 signaling, LTP, and memory, revealing a non-PDZ scaffolding pathway for NR2A.

    Evidence Co-IP from brain; surface NR2A assays and ERK activity in IQGAP1−/− neurons; LTP and behavior

    PMID:21653857

    Open questions at the time
    • Whether IQGAP1 binds NR2A directly or through intermediary unknown
    • Mechanism by which IQGAP1 maintains surface NR2A not resolved
  12. 2013 High

    Demonstrating CPE-dependent local translation of GluN2A mRNA in dendrites established that activity-induced GluN2A surface insertion relies on dendritic protein synthesis rather than solely on somatic supply.

    Evidence Microfluidic compartmentalization, live mRNA translation imaging, and CPE mutagenesis in hippocampal neurons

    PMID:23678131

    Open questions at the time
    • Identity of the RNA-binding protein mediating CPE-dependent GluN2A translation not determined
    • Whether local translation contributes to synapse-specific NR2A insertion unclear
  13. 2014 High

    Selective expression of GluN1/GluN2A/GluN2B triheteromeric receptors revealed their unique kinetic and pharmacological properties, establishing that the majority of brain NMDARs are not simple diheteromers.

    Evidence Engineered cell-surface expression system for triheteromers; patch-clamp in HEK cells with subunit-selective antagonists

    PMID:24607230

    Open questions at the time
    • Structural basis for altered ifenprodil binding geometry in triheteromers unknown
    • Whether triheteromer properties change with post-translational modification untested
  14. 2014 High

    The de novo L812M gain-of-function mutation and its sensitivity to memantine provided proof-of-concept for precision medicine targeting specific GRIN2A mutations with existing NMDAR antagonists.

    Evidence Whole-cell electrophysiology of GluN2A-L812M; drug screening; clinical correlation of memantine efficacy

    PMID:24839611

    Open questions at the time
    • Long-term clinical outcomes of memantine therapy not established
    • Whether other gain-of-function variants respond similarly untested
  15. 2016 High

    Systematic functional analysis of 25 rare agonist-binding-domain variants revealed that disease mutations alter NMDAR through multiple mechanisms (agonist binding, gating, biogenesis, trafficking), establishing that variant impact cannot be predicted from location alone.

    Evidence Recombinant receptor electrophysiology, trafficking, and biogenesis assays for each variant

    PMID:27839871

    Open questions at the time
    • Many variants tested in diheteromeric context only; triheteromer effects unknown
    • Whether variants affect interacting-protein binding not assessed
  16. 2018 High

    Cryo-EM structures of GluN1/GluN2A resolved how zinc binding at the amino-terminal domain propagates through the ligand-binding domain to constrict the channel gate, providing the first atomic-level mechanism for allosteric inhibition of NMDA receptors.

    Evidence Cryo-EM of GluN1/GluN2A under varying zinc and proton concentrations; multiple conformational states resolved

    PMID:30500536

    Open questions at the time
    • Full gating cycle not captured in structures
    • Structural basis of proton vs. zinc inhibition divergence at low occupancy unclear
  17. 2019 High

    A genotype-phenotype analysis of 248 patients combined with systematic electrophysiology established the domain-dependent directionality rule: transmembrane/linker variants cause gain-of-function while ATD/LBD/null variants cause loss-of-function, enabling clinical severity prediction from variant location.

    Evidence Recombinant receptor electrophysiology of disease variants; Grin2a+/− rat cortical neuron recordings; genotype-phenotype correlation in patient cohort

    PMID:30544257

    Open questions at the time
    • Triheteromer context not assessed for most variants
    • Longitudinal clinical validation of severity predictions incomplete
  18. 2019 High

    Calmodulin-mediated Ca²⁺-dependent inactivation was shown to be more prominent in GluN2A receptors due to their higher open probability, revealing an intrinsic negative-feedback mechanism limiting Ca²⁺ entry through high-activity NR2A channels.

    Evidence Single-channel recordings with simultaneous fluorometric Ca²⁺ monitoring in HEK-293 cells; high-Po GluN2B mutant comparison

    PMID:31629478

    Open questions at the time
    • Physiological relevance of CDI at native GluN2A synapses not directly demonstrated
    • Whether CDI interacts with phosphorylation-dependent regulation unclear
  19. 2020 High

    Grin2a-S644G knock-in mice developed lethal seizures rescued by NMDAR antagonists, providing in vivo validation that specific gain-of-function GRIN2A variants are directly causative for epileptic encephalopathy.

    Evidence Knock-in mice; heterologous and hippocampal slice electrophysiology; chronic NMDAR antagonist treatment

    PMID:32577763

    Open questions at the time
    • Optimal therapeutic window and antagonist selectivity for chronic treatment not defined
    • Circuit-level mechanisms linking enhanced NMDAR to seizure initiation not mapped
  20. 2021 High

    Identification of CaMKIIα phosphorylation at GluN2A-Ser1459 promoting SNX27-retromer-mediated endosomal recycling during LTP revealed the first activity-dependent trafficking pathway specific to GluN2A surface delivery, and showed that the epilepsy-associated S1459G variant prolongs channel open time.

    Evidence In vitro kinase assay, co-IP, SNX27/CaMKIIα loss-of-function, S1459A/S1459G mutagenesis with electrophysiology

    PMID:34186182

    Open questions at the time
    • Whether SNX27-retromer is the sole recycling pathway for GluN2A unknown
    • In vivo validation of S1459 phosphorylation dynamics during LTP not performed
  21. 2021 High

    Cryo-EM structures with competitive antagonists and a positive allosteric modulator mapped how ligand binding in different domains translates to gate opening or closure, revealing an unexpected 'foot-in-the-door' blocker cavity in the LBD-TMD linker region.

    Evidence Cryo-EM of full-length human GluN1-GluN2A with multiple ligands at ~4 Å resolution

    PMID:34186027

    Open questions at the time
    • Dynamic gating transitions not captured by static structures
    • Whether foot-in-the-door mechanism is exploitable therapeutically untested
  22. 2022 High

    Discovery that a KKK ER-retention motif controls GluN2A forward trafficking, and its disruption (K879R) elevates synaptic NR2A to impair both LTP and LTD causing intellectual disability, identified a previously unknown quality-control checkpoint for GluN2A biogenesis.

    Evidence KKK motif mutagenesis; surface expression assays; K879R knock-in mice with LTP/LTD and behavioral analysis

    PMID:35484243

    Open questions at the time
    • ER chaperone or co-receptor recognizing the KKK motif not identified
    • Whether the motif interacts with COPI-dependent retrieval unknown
  23. 2023 High

    Loss of Grin2a delays parvalbumin interneuron electrophysiological maturation in a gene-dosage-dependent manner, mechanistically linking GRIN2A haploinsufficiency to transient developmental seizure susceptibility through impaired inhibitory circuit maturation.

    Evidence PV interneuron electrophysiology across development in Grin2a+/−, Grin2a−/−, and WT mice

    PMID:37723282

    Open questions at the time
    • Whether GluN2A acts cell-autonomously in PV interneurons or via network effects unknown
    • Molecular mechanism linking GluN2A to PV cell maturation not identified
  24. 2024 Medium

    A Pyk2→Src→GluN2A-Y1325 phosphorylation feed-forward loop was identified as the mechanism sustaining GluN2A channel activity during homocysteine-induced neurotoxicity, with failure of the phosphatase STEP to counteract the cycle, linking NR2A-specific Ca²⁺ signaling to mitochondrial ROS via ERK MAPK.

    Evidence Live-cell Ca²⁺ imaging, Src/Pyk2 inhibitors, STEP analysis, mitochondrial redox imaging in cortical neurons

    PMID:38569938

    Open questions at the time
    • Whether the feed-forward loop operates during physiological NMDAR activation unknown
    • Single lab; independent replication needed
    • Structural basis for STEP failure to dephosphorylate Y1325 in this context not established
  25. 2024 Medium

    Epitranscriptomic regulation of GluN2A was revealed: METTL14-mediated m6A methylation of GRIN2A mRNA, read by IGF2BP2, stabilizes GluN2A expression in DRG neurons to maintain chemotherapy-induced neuropathic pain.

    Evidence METTL14 gain/loss-of-function, dot blotting for m6A, behavioral pain assays in CINP model, human DRG validation

    PMID:38319733

    Open questions at the time
    • Specific m6A sites on GRIN2A mRNA not mapped
    • Whether m6A regulation of GRIN2A operates in CNS neurons unknown
    • Single lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full gating cycle captured structurally for GluN2A-containing receptors, the identity of the C-terminal effectors that mediate LTP suppression, how triheteromeric receptor properties are regulated in vivo, and whether precision-medicine strategies targeting gain- vs. loss-of-function variants can produce sustained clinical benefit.
  • Complete structural gating cycle not resolved
  • C-terminal domain interaction partners mediating LTP suppression unidentified
  • Triheteromer regulation in native synapses poorly understood
  • Clinical trials for variant-specific NMDAR therapies lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 3 R-HSA-9609507 Protein localization 3
Partners
CAMK2ADLG1DLG4GRIN1GRIN2BIQGAP1KIF3BSNX27
Complex memberships
GluN1/GluN2A NMDA receptorGluN1/GluN2A/GluN2B triheteromeric NMDA receptor

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NR2A subunit expression directly shortens NMDA receptor synaptic current duration in developing neocortex; single neurons expressing NR2A mRNA had faster NMDAR EPSCs than those lacking it, providing a molecular basis for the developmental decrease in NMDAR EPSC duration. Single-cell RT-PCR combined with patch-clamp recordings of identified cortical neurons in postnatal neocortex The Journal of neuroscience High 9065507
1993 NR1 and NR2A subunits co-assemble in HEK293 cells to form a heteromeric complex with pharmacological properties similar to native adult forebrain NMDA receptors, showing a 10-fold increase in [3H]MK801 binding sites over single-subunit expression. Transient co-expression in HEK293 cells, [3H]MK801 radioligand binding, immunoblotting with subunit-specific antibodies, N-deglycosylation The Biochemical journal High 7904155
2005 NR2A-containing NMDA receptors have higher peak open probability (0.50 vs 0.12), higher probability of opening to a synaptic-like glutamate pulse (0.80 vs 0.56), and faster conformational transitions prior to channel opening compared to NR2B-containing receptors, producing distinct temporal signaling profiles. Single-channel patch-clamp recordings from outside-out patches of recombinant NR1/NR2A and NR1/NR2B receptors in HEK293 cells; kinetic modeling and synaptic simulations The Journal of physiology High 15649985
2006 NR2A-containing NMDARs are more stable at the neuronal surface than NR2B-containing NMDARs; NR2A subunit overexpression stabilizes surface NR2B-containing NMDARs, and the developmental increase in synaptic NR2A correlates with longer synaptic dwell times. Single-particle and single-molecule tracking using specific antibodies against NR2A and NR2B extracellular epitopes in cultured neurons Proceedings of the National Academy of Sciences of the United States of America High 17124177
2003 SAP97 directly interacts with the NR2A subunit of the NMDA receptor via its PDZ1 domain; CaMKII-dependent phosphorylation of SAP97 at Ser-232 disrupts the SAP97/NR2A interaction, providing a mechanism for regulated synaptic targeting of NMDA receptors. Co-immunoprecipitation from hippocampal homogenates and synaptosomes, in vitro pull-down assay, metabolic labeling, site-directed mutagenesis (SAP97-S232D), transfection in COS-7 cells The Journal of biological chemistry High 12933808
2010 The NR2A cytoplasmic C-terminal tail plays an inhibitory role in LTP: an NR2A construct lacking its entire C-terminal tail rescued LTP in NR2B-knockdown neurons, whereas wild-type NR2A did not, demonstrating that the NR2A tail suppresses LTP induction. RNAi knockdown and overexpression of wild-type, chimeric, and C-terminal deletion constructs of NR2A/NR2B in organotypic hippocampal slice cultures; electrophysiological LTP recordings The Journal of neuroscience High 20164351
2010 The GRIN2A missense mutation p.N615K causes loss of Mg2+ block and decreased Ca2+ permeability of NR1-NR2A(N615K) receptors, demonstrating that this residue in the channel pore is critical for Mg2+ block and Ca2+ selectivity. In vitro expression and whole-cell electrophysiology (two-electrode voltage clamp) of recombinant NR1-NR2A(N615K) receptors Nature genetics High 20890276
2014 GluN1/GluN2A/GluN2B triheteromeric NMDA receptors have distinct glutamate deactivation kinetics from diheteromers and exhibit differential modulation by subunit-selective antagonists (ifenprodil, CP-101,606, TCN-201) and extracellular Zn2+, with altered ifenprodil binding site geometry compared to GluN1/GluN2B diheteromers. Selective cell-surface expression system for recombinant triheteromers; patch-clamp electrophysiology; kinetic measurements in HEK cells Neuron High 24607230
2018 Cryo-EM structures of GluN1/GluN2A NMDA receptor reveal that zinc binds to the GluN2A amino-terminal domain and elicits structural changes transduced through the ligand-binding domain to constrict the ion channel gate; proton inhibition acts through the same structural pathway. Cryo-electron microscopy of GluN1/GluN2A under varying zinc and proton concentrations; structural analysis of multiple conformational states Cell High 30500536
2021 Cryo-EM structures of human GluN1-GluN2A NMDA receptor reveal competitive antagonist binding to GluN1 and GluN2A ligand-binding domains, a positive allosteric modulator binding that shortens the LBD-TMD distance and opens the gate, and a 'foot-in-the-door' blocker (9-aminoacridine) binding cavity within the LBD-TMD linker region rather than in the TMD vestibule. Cryo-EM of full-length human GluN1-GluN2A with distinct ligands/modulators at ~4 Å resolution Neuron High 34186027
2011 High-affinity (nanomolar) zinc inhibition of NMDA currents is mediated specifically through NR2A; NR2A-H128S knock-in mice lacking this high-affinity zinc binding site show hypersensitivity to pain and loss of zinc-induced analgesia, establishing NR2A as the molecular target for zinc modulation of pain processing in vivo. NR2A-H128S knock-in mouse generation; electrophysiology in hippocampal and spinal cord slices; behavioral pain assays (radiant heat, capsaicin, inflammatory and neuropathic pain models) Nature neuroscience High 21725314
1997 NR2A and NR2B subunits of the NMDA receptor are tyrosine-phosphorylated and bind to the SH2 domains of phospholipase C-gamma in a phosphorylation-dependent manner, linking NMDA receptor tyrosine phosphorylation to PLC-gamma signaling at the synapse. GST-SH2 domain pull-down from synaptic junctional proteins, immunoblotting with subunit-specific antibodies, immunoprecipitation, in vitro kinase assay with ATP and protein tyrosine phosphatase Journal of neurochemistry Medium 9231720
2009 Tyrosine phosphorylation of NR2A at Tyr-1325 regulates NMDA receptor channel activity and depression-related behavior; knock-in mice with Y1325F mutation show antidepressant-like behavior, increased DARPP-32 phosphorylation at Thr-34 in the striatum, and loss of Src-induced potentiation of NMDA receptor channel activity in the striatum. Generation of NR2A-Y1325F knock-in mice; behavioral tests (tail suspension, forced swim); biochemical analysis of DARPP-32 phosphorylation; electrophysiology in striatal neurons The EMBO journal High 19834457
2013 Dendritic protein synthesis is required for activity-induced insertion of GluN2A-containing NMDA receptors; GluN2A mRNA is locally translated in dendrites via a cytoplasmic polyadenylation element (CPE) in its 3' UTR, and this translation is necessary for activity-induced GluN2A surface expression. Microfluidic devices to isolate dendritic compartments, live imaging of GluN2A mRNA translation and GluN2A protein membrane insertion, CPE deletion/mutation analysis in rat hippocampal neurons The Journal of neuroscience High 23678131
2011 KIF3B kinesin transports vesicles simultaneously containing NR2A and the APC complex; Kif3b+/- neurons show reduced dendritic NR2A and NR2B levels due to impaired NR2A transport and increased NR2B degradation, with decreased NMDAR electrophysiological response and disrupted synaptic plasticity. Kif3b+/- mouse model; co-immunoprecipitation of NR2A with KIF3B and APC; electrophysiology in hippocampal slices; behavioral assays; genetic rescue experiment with human KIF3B mutation The EMBO journal High 31746486
2021 CaMKIIα phosphorylates GluN2A at Ser-1459 in response to LTP-mimicking stimulation; this phosphorylation promotes GluN2A interaction with the SNX27-retromer complex to enhance endosomal recycling and NMDAR membrane insertion. The S1459G epilepsy variant prolongs NMDAR synaptic current decay by increasing channel open duration. In vitro kinase assay, co-immunoprecipitation, loss-of-function of SNX27 and CaMKIIα, site-directed mutagenesis (S1459A, S1459G), heterosynapse electrophysiology in primary neurons Cell reports High 34233182
2016 Rare missense variants in the GluN2A agonist binding domain dysregulate NMDAR activity through multiple distinct mechanisms including altered agonist binding, channel gating, receptor biogenesis, and forward trafficking; these combined effects determine net impact on synaptic vs. non-synaptic NMDAR function. Recombinant expression of 25 rare GluN2A agonist-binding domain variants in human NMDARs; two-electrode voltage clamp, whole-cell patch clamp, receptor trafficking assays, biogenesis assays American journal of human genetics High 27839871
2014 The de novo GRIN2A mutation p.L812M increases charge transfer through NMDA receptors containing mutant GluN2A-L812M, and these receptors retain sensitivity to the channel blocker memantine, which when used clinically reduced seizure burden in the patient. In vitro expression and whole-cell electrophysiology of mutant GluN2A-L812M; drug library screening; clinical correlation Annals of clinical and translational neurology High 24839611
2017 The de novo GRIN2A mutation p.M817V in the pre-M4 linker causes gain-of-function: enhanced agonist potency, reduced sensitivity to Mg2+, protons and zinc, prolonged synaptic response time course, increased single-channel mean open time and open probability; molecular modeling shows the mutation weakens GluN2 M4 helix interactions with GluN1 transmembrane helices. Whole-cell voltage clamp, single-channel recordings, two-electrode voltage clamp in Xenopus oocytes, molecular modeling of closed-channel conformation Molecular pharmacology High 28126851
2019 Missense variants in GluN2A transmembrane and linker domains predominantly cause NMDA receptor gain-of-function, while variants in the amino-terminal or ligand-binding domains and null variants cause loss-of-function; Grin2a+/- cortical rat neurons have reduced NMDAR function without compensatory GluN2B upregulation. Electrophysiology of recombinant receptors with disease-associated variants; primary cortical neuron recordings from Grin2a+/- rats; genotype-phenotype analysis in 248 patients Brain : a journal of neurology High 30544257
2004 PSD-95 increases current response of both NR1-NR2A and NR1-NR2B receptors, while MALS-2 increases NR1-NR2B but not NR1-NR2A current; PSD-95 inhibits protein kinase C- and Src-mediated potentiation of NR1-NR2A activity through distinct PDZ domain mechanisms, revealing differential modulation of NR2A-containing receptors by PDZ proteins. Xenopus oocyte expression of NMDA receptor subunits with MALS-2 or PSD-95; two-electrode voltage clamp; PDZ domain chimera constructs Journal of neurochemistry High 15030393
2011 IQGAP1 forms part of NMDAR multiprotein complexes and functionally interacts with NR2A subunits; IQGAP1 knockout reduces surface NR2A levels and disrupts ERK1/2 signaling downstream of NR2A-dependent NMDAR stimulation, impairing hippocampal LTP and long-term memory. Co-immunoprecipitation from brain tissue; surface NR2A measurement in IQGAP1-/- hippocampal neurons; ERK activity assays; LTP recordings in hippocampal slices; behavioral memory tests The Journal of neuroscience High 21653857
2019 Ca2+-dependent inactivation (CDI) of GluN2A-type NMDA receptors, mediated by calmodulin binding to GluN1, causes receptor accumulation in long-lived closed/desensitized states; GluN2B receptors show minimal CDI in physiological external Ca2+ due to their lower open probability, but show robust CDI when Ca2+ is supplied intracellularly, indicating CDI mechanism is common to both subtypes. Whole-cell patch clamp of recombinant NMDARs in HEK-293 cells; single-channel recordings with simultaneous fluorometric Ca2+ monitoring; high-Po GluN2B mutant analysis Biophysical journal High 31629478
2020 Lupus autoantibodies (DNRAbs) act as positive allosteric modulators specifically on GluN2A-containing NMDARs (including triheteromers with a single GluN2A subunit); GluN2A-specific antagonists provide greater protection from DNRAb-mediated neuronal cell death, and DNRAb-mediated disruption of spatial memory requires GluN2A-containing NMDARs. Electrophysiology of recombinant NMDARs; GluN2A/GluN2B transgenic mice with in vivo DNRAb exposure; subunit-selective antagonists; behavioral spatial memory tests; neuronal death assays Nature communications High 32179753
2016 MicroRNA-139-5p negatively regulates NR2A (but not NR2B) expression by targeting GRIN2A; overexpression of miR-139-5p decreases NR2A protein levels while its depletion enhances NR2A expression in the pilocarpine model of temporal lobe epilepsy. miRNA microarray, qRT-PCR, Western blot; miR-139-5p agomir and antagomir delivery in vivo in rat pilocarpine model; patient hippocampal tissue analysis Epilepsia Medium 27731509
2016 GluN2A subunit mediates NR2A-NMDAR-activated neuronal NMDA receptor-induced microglia-neuron physical interactions in adult hippocampus; GluN2A inhibitor (NVP-AAM077) but not GluN2B inhibitor (ifenprodil) blocked these interactions, which were absent in neonatal tissue consistent with the developmental regulation of GluN2A. Two-photon in vivo imaging; subunit-selective pharmacological inhibitors; developmental comparison; hippocampal region-specific analysis Scientific reports Medium 29339791
2019 Alpha-synuclein selectively reduces GluN2A NMDA receptor subunit function and synaptic localization in striatal spiny projection neurons, impairing corticostriatal LTP; antibodies targeting alpha-synuclein prevent this GluN2A loss and restore LTP. Electrophysiology, optogenetics, immunofluorescence, molecular and behavioral analyses in in vitro and ex vivo striatal preparations with alpha-synuclein application Brain : a journal of neurology Medium 30927362
2016 NMDARs adapt to neurotoxic HIV Tat protein via a GluN2A-containing NMDAR/Akt/Mdm2 signaling pathway; GluN2A activation triggers Akt phosphorylation, which activates E3 ubiquitin ligase Mdm2 to degrade PSD-95, causing loss of NMDAR synaptic clusters and adaptation of NMDAR currents. Patch-clamp recording of NMDAR-mediated currents; pharmacological and genetic inhibition of GluN2A, Akt, and Mdm2; GFP-tagged GluN1 puncta analysis in rat hippocampal cultures The Journal of neuroscience Medium 27810933
2019 Homocysteine-induced neurotoxicity is mediated specifically through GluN2A-NMDAR: homocysteine causes sustained low-level Ca2+ influx via GluN2A-NMDARs, which activates sustained ERK MAPK phosphorylation and neuronal death; this mechanism is distinct from glutamate-induced excitotoxicity that involves GluN2B-NMDAR. GluN2A-selective pharmacological inhibition and GluN2A genetic deletion in primary cortical neuronal cultures; Ca2+ imaging; ERK phosphorylation assays; cell death assays The Journal of biological chemistry Medium 31167782
2024 GluN2A-NMDAR-mediated sustained Ca2+ influx maintains channel activity through a feed-forward cycle: initial Ca2+ influx activates Pyk2, which activates Src family kinases, which phosphorylate GluN2A at Tyr-1325 to maintain channel activity; the tyrosine phosphatase STEP fails to limit this cycle, leading to mitochondrial ROS generation via ERK MAPK. Live-cell Ca2+ imaging (Fluo3-AM), biochemical phosphorylation assays, Src/Pyk2 inhibitors, STEP analysis, mitochondrial ROS imaging with redox-sensitive GFP in neurons The Journal of biological chemistry Medium 38569938
2020 De novo GRIN2A knock-in mice (p.Ser644Gly) show enhanced NMDAR agonist potency and prolonged synaptic NMDAR current deactivation in hippocampal slices; homozygous mice develop lethal seizures, and NMDAR antagonists delayed seizure onset, establishing gain-of-function S644G as causative for epileptic encephalopathy. Grin2a knock-in mouse generation; heterologous cell electrophysiology; hippocampal slice NMDAR-EPSC recordings; multielectrode array; behavioral phenotyping; chronic NMDAR antagonist treatment Brain : a journal of neurology High 32577763
2023 Loss of Grin2a causes age- and gene-dosage-dependent transient delays in electrophysiological maturation of parvalbumin (PV) interneurons in CA1, with Grin2a-/- mice not reaching PV cell maturation until adulthood; this delay in inhibitory circuit maturation underlies the transient seizure susceptibility seen in null GRIN2A patients. Electrophysiological characterization of PV interneurons across developmental ages in Grin2a+/-, Grin2a-/- and wild-type mice; CA1 pyramidal cell output recordings; developmental time-course analysis Communications biology High 37723282
2022 A GluN2A K879R mutation disrupts a KKK ER retention motif, enhancing GluN2A surface expression; elevated synaptic GluN2A-NMDAR impairs LTP and LTD and causes intellectual disability, demonstrating that the KKK motif regulates GluN2A ER retention and forward trafficking. Site-directed mutagenesis of KKK motif; surface expression assays; patch-clamp recording of EPSCs in CA1 neurons; GluN2A_K879R knock-in mice; LTP/LTD recordings; behavioral memory tests Molecular psychiatry High 35484243
2024 METTL14-mediated m6A methylation of GRIN2A mRNA, read by IGF2BP2, stabilizes GluN2A expression in DRG neurons and promotes presynaptic NMDAR activity to maintain chemotherapy-induced neuropathic pain; blocking METTL14 reduces m6A methylation and attenuates pain hypersensitivity. Dot blotting, immunofluorescence, gain/loss-of-function of METTL14, behavioral pain assays in CINP model; human DRG validation The Journal of clinical investigation Medium 38319733
2014 Somatic mutations in GRIN2A in melanoma cause loss of NMDAR complex formation between GRIN1 and GRIN2A (dominant negative effect), increase anchorage-independent growth and cell migration; depletion of wild-type GRIN2A in melanoma cells increases proliferation, establishing GRIN2A as a tumor suppressor in melanoma. Functional characterization of GRIN2A mutants: co-immunoprecipitation for complex formation, soft agar anchorage-independent growth, migration assays, shRNA knockdown in melanoma cell lines The Journal of investigative dermatology Medium 24739903
2024 SCZ-associated GRIN2A variants are predominantly loss-of-function, whereas epilepsy/DD/ID-associated variants cause both gain- and loss-of-function; specific LoF variants (M653I, S809R) associated with DD/ID exert dominant-negative effects when co-expressed with wild-type GluN2A, while SCZ-linked LoF variants (E58Ter, Y698C) do not. Recombinant expression of GluN1/GluN2A heteromeric receptors in HEK cells; whole-cell patch clamp electrophysiology; co-expression with wild-type GluN2A to test dominant-negative effects Scientific reports Medium 38307912
2021 Voltage-independent Ca2+ signaling through GluN2A-containing NMDARs (Grin2aN615S knock-in) causes audiogenic seizures from hyperexcitable midbrain circuits and reduces hippocampal theta/gamma synchronization during exploration, demonstrating that voltage-dependent Ca2+ influx through GluN2A is essential for proper sensory response tuning and hippocampal circuit function. Grin2aN615S knock-in mice; in vivo EEG oscillation recordings; c-Fos expression after MK-801; behavioral assays; audiogenic seizure induction Communications biology High 33420383

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 NR2A subunit expression shortens NMDA receptor synaptic currents in developing neocortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 499 9065507
2010 Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes. Nature genetics 402 20890276
2011 Exome sequencing identifies GRIN2A as frequently mutated in melanoma. Nature genetics 388 21499247
2005 Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. The Journal of physiology 341 15649985
2006 NMDA receptor surface mobility depends on NR2A-2B subunits. Proceedings of the National Academy of Sciences of the United States of America 294 17124177
2014 Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors. Neuron 260 24607230
2014 GRIN2A mutation and early-onset epileptic encephalopathy: personalized therapy with memantine. Annals of clinical and translational neurology 205 24839611
2010 Distinct roles of NR2A and NR2B cytoplasmic tails in long-term potentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 179 20164351
2019 GRIN2A-related disorders: genotype and functional consequence predict phenotype. Brain : a journal of neurology 172 30544257
2016 Mechanistic Insight into NMDA Receptor Dysregulation by Rare Variants in the GluN2A and GluN2B Agonist Binding Domains. American journal of human genetics 144 27839871
1995 Distribution of NMDA receptor subunit proteins NR2A, 2B, 2C and 2D in rat brain. Neuroreport 137 8742413
2008 Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit. Learning & memory (Cold Spring Harbor, N.Y.) 133 18230672
2006 Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain research 124 17113057
2010 Identification and characterization of novel NMDA receptor antagonists selective for NR2A- over NR2B-containing receptors. The Journal of pharmacology and experimental therapeutics 122 20810618
2007 Excitotoxicity in vitro by NR2A- and NR2B-containing NMDA receptors. Neuropharmacology 120 17570444
2008 Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. The international journal of neuropsychopharmacology 113 18570704
2019 Distinct roles of GRIN2A and GRIN2B variants in neurological conditions. F1000Research 111 31807283
1993 Optimal expression of cloned NMDAR1/NMDAR2A heteromeric glutamate receptors: a biochemical characterization. The Biochemical journal 110 7904155
2018 Mechanisms for Zinc and Proton Inhibition of the GluN1/GluN2A NMDA Receptor. Cell 103 30500536
2011 Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nature neuroscience 99 21725314
2019 Alpha-synuclein targets GluN2A NMDA receptor subunit causing striatal synaptic dysfunction and visuospatial memory alteration. Brain : a journal of neurology 94 30927362
2005 Autoantibodies to a NR2A peptide of the glutamate/NMDA receptor in sera of patients with systemic lupus erythematosus. Annals of the rheumatic diseases 93 15708887
2003 CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction. The Journal of biological chemistry 87 12933808
2011 IQGAP1 regulates NR2A signaling, spine density, and cognitive processes. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 21653857
2009 Involvement of NMDAR2A tyrosine phosphorylation in depression-related behaviour. The EMBO journal 76 19834457
2010 Activation of NR2A receptors induces ischemic tolerance through CREB signaling. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 75 20145658
2005 Roles of NMDA receptor NR2A and NR2B subtypes for long-term depression in the anterior cingulate cortex. The European journal of neuroscience 67 16045501
2017 Functional Evaluation of a De Novo GRIN2A Mutation Identified in a Patient with Profound Global Developmental Delay and Refractory Epilepsy. Molecular pharmacology 66 28126851
2020 Modelling and treating GRIN2A developmental and epileptic encephalopathy in mice. Brain : a journal of neurology 64 32577763
2015 GRIN2A: an aptly named gene for speech dysfunction. Neurology 56 25596506
2004 Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region. Molecular psychiatry 56 14699423
2021 Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron 55 34186027
2013 Involvement of NR1, NR2A different expression in brain regions in anxiety-like behavior of prenatally stressed offspring. Behavioural brain research 55 24029697
2023 Brain-region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice. Neuron 54 37657442
2012 Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders. Neuroscience letters 53 22326929
1999 Selective coexpression of NMDAR2A/B and NMDAR1 subunit proteins in dysplastic neurons of human epileptic cortex. Experimental neurology 53 10506512
2017 A de novo loss-of-function GRIN2A mutation associated with childhood focal epilepsy and acquired epileptic aphasia. PloS one 52 28182669
2018 The differences between GluN2A and GluN2B signaling in the brain. Journal of neuroscience research 51 29682799
2020 Lupus autoantibodies act as positive allosteric modulators at GluN2A-containing NMDA receptors and impair spatial memory. Nature communications 48 32179753
2019 Melatonin Protects MCAO-Induced Neuronal Loss via NR2A Mediated Prosurvival Pathways. Frontiers in pharmacology 48 31024297
2019 Kinesin Kif3b mutation reduces NMDAR subunit NR2A trafficking and causes schizophrenia-like phenotypes in mice. The EMBO journal 48 31746486
1997 The N-methyl-D-aspartate receptor subunits NR2A and NR2B bind to the SH2 domains of phospholipase C-gamma. Journal of neurochemistry 48 9231720
2023 GRIN2A (NR2A): a gene contributing to glutamatergic involvement in schizophrenia. Molecular psychiatry 47 37736757
2023 Mouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients. Translational psychiatry 46 36914641
2013 Dendritic GluN2A synthesis mediates activity-induced NMDA receptor insertion. The Journal of neuroscience : the official journal of the Society for Neuroscience 46 23678131
2019 GluN2A-NMDA receptor-mediated sustained Ca2+ influx leads to homocysteine-induced neuronal cell death. The Journal of biological chemistry 45 31167782
2018 The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron Physical Interactions. Scientific reports 45 29339791
2017 GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat. Frontiers in behavioral neuroscience 45 28133447
2009 Increased expression of the NR2A NMDA receptor subunit in the prefrontal cortex of rats reared in isolation. Synapse (New York, N.Y.) 40 19533626
2011 Association of GRIN1 and GRIN2A-D with schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 39 21919190
2024 METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2. The Journal of clinical investigation 36 38319733
2004 Differential modulation of NR1-NR2A and NR1-NR2B subtypes of NMDA receptor by PDZ domain-containing proteins. Journal of neurochemistry 36 15030393
2019 Update on the genetics of the epilepsy-aphasia spectrum and role of GRIN2A mutations. Epileptic disorders : international epilepsy journal with videotape 34 31149903
2016 The Functional and Molecular Properties, Physiological Functions, and Pathophysiological Roles of GluN2A in the Central Nervous System. Molecular neurobiology 34 26797520
2021 Knockdown of astrocytic Grin2a aggravates β-amyloid-induced memory and cognitive deficits through regulating nerve growth factor. Aging cell 33 34291567
2016 Astrocytic GluN2A and GluN2B Oppose the Synaptotoxic Effects of Amyloid-β1-40 in Hippocampal Cells. Journal of Alzheimer's disease : JAD 33 27497478
2016 MicroRNA-139-5p negatively regulates NR2A-containing NMDA receptor in the rat pilocarpine model and patients with temporal lobe epilepsy. Epilepsia 33 27731509
2022 Enhancing GluN2A-type NMDA receptors impairs long-term synaptic plasticity and learning and memory. Molecular psychiatry 32 35484243
2019 Memory and plasticity impairment after binge drinking in adolescent rat hippocampus: GluN2A/GluN2B NMDA receptor subunits imbalance through HDAC2. Addiction biology 31 31056842
2014 Somatic mutation of GRIN2A in malignant melanoma results in loss of tumor suppressor activity via aberrant NMDAR complex formation. The Journal of investigative dermatology 31 24739903
2023 Loss of Grin2a causes a transient delay in the electrophysiological maturation of hippocampal parvalbumin interneurons. Communications biology 30 37723282
2021 Voltage-independent GluN2A-type NMDA receptor Ca2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice. Communications biology 30 33420383
2018 Disruption of the NMDA receptor GluN2A subunit abolishes inflammation-induced depression. Behavioural brain research 30 30296532
2015 Dissociable effects of NR2A and NR2B NMDA receptor antagonism on cognitive flexibility but not pattern separation. Psychopharmacology 30 26184010
1993 Characterization of the NR1, NR2A, and NR2C receptor proteins. Protein science : a publication of the Protein Society 29 8298456
2018 A novel missense mutation in GRIN2A causes a nonepileptic neurodevelopmental disorder. Movement disorders : official journal of the Movement Disorder Society 28 29644724
2022 De novo GRIN2A variants associated with epilepsy and autism and literature review. Epilepsy & behavior : E&B 27 35217385
2021 Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit. Cell reports 27 34233182
2015 Association between GRIN2A promoter polymorphism and recovery from concussion. Brain injury 27 26502998
2004 Pharmacological and genetic evidence indicates that combined inhibition of NR2A and NR2B subunit containing NMDA receptors is required to disrupt prepulse inhibition. Psychopharmacology 26 14985927
2024 Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology. Physiological research 25 38836461
2019 Ca2+-Dependent Inactivation of GluN2A and GluN2B NMDA Receptors Occurs by a Common Kinetic Mechanism. Biophysical journal 25 31629478
2014 Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population. PloS one 25 24915238
2022 Common synaptic phenotypes arising from diverse mutations in the human NMDA receptor subunit GluN2A. Communications biology 24 35228668
2014 Loss of GluN2A-containing NMDA receptors impairs extra-dimensional set-shifting. Genes, brain, and behavior 24 25059550
2013 Two patients with a GRIN2A mutation and childhood-onset epilepsy. Pediatric neurology 24 24125812
2015 Correlation of functional GRIN2A gene promoter polymorphisms with schizophrenia and serum D-serine levels. Gene 23 25958346
2015 Different sites of alcohol action in the NMDA receptor GluN2A and GluN2B subunits. Neuropharmacology 23 26051400
2014 Evidence That GRIN2A Mutations in Melanoma Correlate with Decreased Survival. Frontiers in oncology 23 24455489
2021 Reduced Expression of Hippocampal GluN2A-NMDAR Increases Seizure Susceptibility and Causes Deficits in Contextual Memory. Frontiers in neuroscience 22 33897358
2017 Caffeine, creatine, GRIN2A and Parkinson's disease progression. Journal of the neurological sciences 22 28320167
2016 The GRIN2B and GRIN2A Gene Variants Are Associated With Continuous Performance Test Variables in ADHD. Journal of attention disorders 22 27199241
2021 Study of Early Onset Schizophrenia: Associations of GRIN2A and GRIN2B Polymorphisms. Life (Basel, Switzerland) 21 34685369
2018 Inhibition of GluN2A NMDA receptors ameliorates synaptic plasticity deficits in the Fmr1-/y mouse model. The Journal of physiology 21 30132892
2016 Response to immunotherapy in a patient with Landau-Kleffner syndrome and GRIN2A mutation. Epileptic disorders : international epilepsy journal with videotape 21 26806548
2016 NR2A- and NR2B-NMDA receptors and drebrin within postsynaptic spines of the hippocampus correlate with hunger-evoked exercise. Brain structure & function 21 27915379
2013 Analysis of variations in the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene reveals their relative importance as genetic susceptibility factors for heroin addiction. PloS one 21 23940648
2011 A genome-wide association study with DNA pooling identifies the variant rs11866328 in the GRIN2A gene that affects disease progression of chronic HBV infection. Viral immunology 21 22004137
2002 Differential NR2A and NR2B expression between trigeminal neurons during early postnatal development. Synapse (New York, N.Y.) 20 11891879
2024 Homocysteine-induced sustained GluN2A NMDA receptor stimulation leads to mitochondrial ROS generation and neurotoxicity. The Journal of biological chemistry 19 38569938
2021 GluN2B and GluN2A-containing NMDAR are differentially involved in extinction memory destabilization and restabilization during reconsolidation. Scientific reports 19 33420399
2017 The Role of GluN2A in Cerebral Ischemia: Promoting Neuron Death and Survival in the Early Stage and Thereafter. Molecular neurobiology 19 28102473
2020 Effects of GluN2A and GluN2B gain-of-function epilepsy mutations on synaptic currents mediated by diheteromeric and triheteromeric NMDA receptors. Neurobiology of disease 18 32247039
2020 GluN2B but Not GluN2A for Basal Dendritic Growth of Cortical Pyramidal Neurons. Frontiers in neuroanatomy 18 33281565
2018 Genetic polymorphisms of GRIN2A and GRIN2B modify the neurobehavioral effects of low-level lead exposure in children. Environmental research 18 29655037
2016 NMDARs Adapt to Neurotoxic HIV Protein Tat Downstream of a GluN2A-Ubiquitin Ligase Signaling Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 27810933
1994 Expression of NMDAR1-1a (N598Q)/NMDAR2A receptors results in decreased cell mortality. European journal of pharmacology 18 7909752
2024 Differential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders. Scientific reports 17 38307912
2017 Systematic variation of the benzenesulfonamide part of the GluN2A selective NMDA receptor antagonist TCN-201. European journal of medicinal chemistry 17 28222314
2015 Investigation of GRIN2A in common epilepsy phenotypes. Epilepsy research 17 26220384