Affinage

GRIN1

Glutamate receptor ionotropic, NMDA 1 · UniProt Q05586

Length
938 aa
Mass
105.4 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 46 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIN1 encodes GluN1, the obligatory subunit of NMDA receptor complexes localized to postsynaptic densities of neurons throughout the hippocampus, cortex, and cerebellum (PMID:8301357). Functional receptors assemble as alternating 1/2/1/2 tetramers in which GluN1 occupies the pore-proximal position relative to GluN2 (PMID:22493736), and GluN1 also forms 1-3-1-3 arrangements with GluN3A (PMID:38598639). Within the complex GluN1 supplies the glycine-binding ligand-binding domain (LBD), whose apo state samples closed-cleft conformations by conformational selection and continues to transition among multiple cleft widths even when glycine is bound (PMID:23972471, PMID:26153703); its N-terminal domain is conformationally dynamic and acts allosterically in trans to influence GluN2-dependent glutamate binding and gating (PMID:23454977). GluN1 exerts global control over channel gating—mutations in its SYTANLAAF gating motif permit activation by NMDA alone (PMID:25339225)—and conformational freedom of its LBD-TMD linkers is required for pore opening, as revealed by cryo-EM structures defining how LBD-TMD crosstalk drives activation, allosteric potentiation, and channel block (PMID:21746848, PMID:34186027). GluN1 alternative splicing tunes receptor behavior: the exon-5 N1 cassette accelerates deactivation, raises open probability, gates nonionotropic glycine-primed internalization, and sets the magnitude of hippocampal LTP and spatial learning (PMID:22641781, PMID:34187890, PMID:31875540), while C-terminal cassettes regulate GluN1/GluN3A activity and pharmacology (PMID:28365212). GluN1/GluN3A receptors gated by glycine alone operate in adult medial habenula and CA1 neurons to control aversive behavior and excitability (PMID:31601771, PMID:30425244). GluN1 abundance and surface delivery are controlled post-transcriptionally—neurofilament light stabilizes GluN1 against ubiquitin-proteasomal turnover (PMID:30143609), the Cullin3 adaptor KCTD13 drives K48-linked polyubiquitination at K860 to set surface receptor levels and seizure threshold (PMID:37142655)—and transcriptionally by Sp4 (via Nwk2) and TFAP2A (PMID:23871830, PMID:25045015, PMID:39009095). GluN1 is directly bound by the σ-1 receptor, partners with D1 dopamine receptors to couple to ERK signaling and plasticity, and associates with α2δ-1, PCDH7, and protons that modulate gating and trafficking (PMID:24227730, PMID:25070539, PMID:38615365, PMID:32616769, PMID:27000430). De novo GRIN1 mutations cause severe neurodevelopmental disorders through either dominant-negative loss of channel function or gain-of-function alterations in agonist potency, Mg2+ block, and trafficking (PMID:27164704, PMID:34227748, PMID:29365063, PMID:37734923). Beyond the nervous system, GluN1-containing NMDA receptors in megakaryocytes regulate proplatelet formation through Ca2+ signaling and cytoskeletal reorganization (PMID:35245376, PMID:28277064).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Establishing where GluN1 acts answered whether it is a synaptic receptor component, placing it at the postsynaptic membrane of central neurons.

    Evidence Ultrastructural immunocytochemistry on rat nervous system sections

    PMID:8301357

    Open questions at the time
    • Did not resolve subunit stoichiometry or partner subunits
    • No functional measurement at characterized synapses
  2. 1995 Medium

    Defining the human GRIN1 gene structure established the genomic basis for the eight splice isoforms and implicated developmental promoter control.

    Evidence Cosmid cloning, sequencing, and FISH mapping of human GRIN1

    PMID:7622053

    Open questions at the time
    • Functional consequences of individual isoforms not tested
    • Homeodomain promoter control inferred from sequence, not assayed
  3. 1998 Medium

    Identifying NRSE/NRSF, single-stranded DNA-binding proteins, and later Sp4/Nwk2 and TFAP2A answered how GluN1 transcription is restricted to neurons and coupled to activity and signaling.

    Evidence Promoter deletion, EMSA, ChIP, reporter assays, and siRNA across cell systems and DRG/SGCs

    PMID:23871830 PMID:25045015 PMID:39009095 PMID:9422773

    Open questions at the time
    • Relative contribution of each factor in vivo unresolved
    • Sp4-Nwk2 surface-trafficking link characterized only in cerebellar granule neurons
  4. 1997 High

    Dissociating mRNA from protein regulation showed GluN1 expression is dominated by post-transcriptional and local-synthesis control rather than transcript abundance.

    Evidence Parallel immunofluorescence and in situ hybridization in PC12 cells, estradiol-treated rats, and lesioned hippocampus

    PMID:8226739 PMID:8824322 PMID:9045729

    Open questions at the time
    • Molecular machinery of local translation not identified
    • Did not pinpoint the post-transcriptional checkpoint
  5. 2013 High

    Defining GluN1 LBD and NTD dynamics answered how the glycine site engages ligand and how the N-terminal domain allosterically tunes gating.

    Evidence X-ray crystallography, smFRET, computational free-energy landscapes, mutagenesis, and electrophysiology of recombinant receptors

    PMID:23454977 PMID:23972471 PMID:24072709 PMID:26153703

    Open questions at the time
    • Link between isolated-domain dynamics and full-length channel gating inferred
    • Functional role of long-lived intermediate cleft states unresolved
  6. 2012 High

    Establishing the 1/2/1/2 arrangement and the requirement for LBD-TMD linker freedom answered how GluN1 is positioned in the tetramer and how it transmits force to the pore.

    Evidence Disulfide cross-linking with functional recording and structural homology modeling

    PMID:21746848 PMID:22493736

    Open questions at the time
    • Mature vs immature arrangement differences not structurally resolved at the time
    • Inter-subunit gating coupling detail limited to engineered constraints
  7. 2014 High

    Showing GluN1 globally controls GluN2 gating and characterizing triheteromers clarified the division of labor among subunits in activation and pharmacology.

    Evidence SYTANLAAF mutagenesis with kinetic analysis; dominant-negative and FRET/FLIM triheteromer expression strategies with pharmacology

    PMID:24607230 PMID:25339225 PMID:29483146

    Open questions at the time
    • Native abundance of specific triheteromers in vivo not quantified
    • Structural basis of asymmetric pore contributions resolved later
  8. 2013 High

    Identifying direct binding of σ-1 receptor and D1 dopamine receptors to GluN1 answered how the receptor is allosterically and signal-transductively coupled to other receptor systems.

    Evidence AFM imaging, co-IP, proximity ligation, blocking peptide, Ca2+/ERK assays, slice electrophysiology, and behavior

    PMID:24227730 PMID:25070539

    Open questions at the time
    • Stoichiometry and structural interface of these complexes unresolved
    • Whether σ-1 and D1R compete or co-occupy GluN1 not addressed
  9. 2016 High

    Functional characterization of de novo GRIN1 variants answered how mutations cause disease, distinguishing dominant-negative loss-of-function from gain-of-function mechanisms.

    Evidence Two-electrode and whole-cell voltage-clamp of variants in oocytes/HEK cells with trafficking and pharmacological profiling, plus clinical genetics

    PMID:27164704 PMID:28228639 PMID:29365063 PMID:34227748 PMID:36341805 PMID:37734923

    Open questions at the time
    • Genotype-to-phenotype prediction across the variant spectrum incomplete
    • In vivo neuronal consequences of each variant not modeled
  10. 2018 High

    Discovering native glycine-gated GluN1/GluN3A receptors and their structural basis answered whether GluN1 supports non-canonical signaling in adult brain.

    Evidence Native and recombinant electrophysiology with CGP-78608, redox manipulation, proton modulation, selective NAMs, viral knockdown, behavior, and cryo-EM

    PMID:27000430 PMID:28365212 PMID:30425244 PMID:31601771 PMID:32389749 PMID:38598639

    Open questions at the time
    • Endogenous ligands and physiological triggers in vivo only partly defined
    • Cell-type distribution of GluN3A-containing receptors incompletely mapped
  11. 2018 High

    Identifying NFL, KCTD13, PCDH7, α2δ-1, and glycine-site structure as regulators answered how GluN1 protein stability and surface delivery are controlled.

    Evidence Co-IP, ubiquitination assays with site mapping, interaction screen, knockout/knockdown mouse and cell models with electrophysiology and trafficking readouts

    PMID:30143609 PMID:31444392 PMID:32616769 PMID:37142655 PMID:38615365

    Open questions at the time
    • Integration of these regulators into a single trafficking pathway unresolved
    • PCDH7 and α2δ-1 mechanisms of NMDAR modulation not fully resolved
  12. 2021 High

    Cryo-EM of full-length human GluN1-GluN2A/C/D and GluN1/GluN3A receptors answered how ligands, allosteric modulators, and blockers act on the assembled receptor.

    Evidence Single-particle cryo-EM in multiple ligand and subunit states with mutagenesis validation

    PMID:34186027 PMID:36309015 PMID:38598639

    Open questions at the time
    • Dynamic gating transitions inferred from static states
    • Triheteromeric receptor structures resolved for limited subunit combinations
  13. 2022 High

    Platelet-lineage Grin1 deletion answered whether GluN1 has a non-neuronal function, revealing a role in megakaryopoiesis and proplatelet formation.

    Evidence Cre-loxP lineage-specific knockout, platelet function and Ca2+ assays, cytoskeletal imaging, antibody inhibition, and bleeding-time measurement

    PMID:28277064 PMID:35245376

    Open questions at the time
    • Subunit composition of megakaryocyte NMDARs not defined
    • Upstream activating ligand in platelet lineage unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many regulators of GluN1 abundance, splicing, and partner assembly are integrated to set receptor composition at specific synapses in vivo remains unresolved.
  • No unified model linking transcriptional, post-transcriptional, and trafficking control
  • Spatiotemporal logic of isoform and GluN2/GluN3 partner selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0005215 transporter activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-1643685 Disease 4 R-HSA-112316 Neuronal System 3 R-HSA-109582 Hemostasis 2 R-HSA-162582 Signal Transduction 2
Partners
CACNA2D1DRD1GRIN2AGRIN3AKCTD13NEFLPCDH7SIGMAR1
Complex memberships
D1R/GluN1 complexGluN1/GluN3A receptorNMDA receptor (GluN1/GluN2)postsynaptic density

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 NMDAR1 (GluN1) protein localizes predominantly to postsynaptic densities in neurons of the hippocampus, cerebral cortex, and cerebellar cortex, as determined by ultrastructural immunolocalization. The major staining was in postsynaptic densities apposed by unstained presynaptic terminals, indicating GluN1 is a postsynaptic component of NMDA receptor complexes. Light and electron microscope immunocytochemistry with selective anti-peptide antibody on rat nervous system sections The Journal of neuroscience High 8301357
1993 In PC12 cells, NMDAR1 mRNA is present but little or no NMDAR1 protein is detectable endogenously, and no functional NMDA-gated ion channels are observed; however, transfection with an NMDAR1 expression vector produces detectable protein. This indicates post-transcriptional regulation controls NMDAR1 protein expression. Northern hybridization, PCR, monoclonal antibody immunoblot, calcium imaging, and patch-clamp recording in PC12 cells; transfection rescue experiment The Journal of biological chemistry High 8226739
1996 Estradiol treatment in ovariectomized rats increases NMDAR1 subunit protein immunofluorescence in CA1 pyramidal cell somata and dendrites without changing NMDAR1 mRNA levels, indicating estradiol modulates NMDA receptor function via post-transcriptional regulation of the GluN1 subunit protein. Confocal laser scanning microscopy for immunofluorescence quantification of NMDAR1 protein; in situ hybridization for NMDAR1 mRNA in rat hippocampal regions The Journal of neuroscience High 8824322
1997 After perforant path transection, NMDAR1 mRNA increases throughout the full dendritic extent of dentate gyrus granule cells (including non-denervated segments), whereas increased NMDAR1 protein is restricted to denervated dendritic segments. This demonstrates that NMDAR1 mRNA is transported into dendrites and that local protein synthesis is regulated independently of mRNA transport in response to synaptic reorganization. Quantitative immunofluorescence and in situ hybridization in rat hippocampus at 2, 5, and 9 days post-lesion The Journal of neuroscience High 9045729
1998 Cell-type-specific transcription of the NMDAR1 gene is controlled by the neuron-restrictive silencer element (NRSE/NRSF) and by single-stranded DNA-binding proteins (SBPs) interacting with a GC-rich/Sp1-containing proximal promoter region. The SBPC2 complex (enriched in neurons) correlates with higher promoter activity; NGF treatment shifts the ratio from SBPC1 to SBPC2 in PC12 cells, suggesting a mechanism for NGF-regulated NMDAR1 transcription. Deletion analysis of NMDAR1 promoter in C6, HeLa, and PC12 cells; EMSA with nuclear proteins; UV cross-linking; competition experiments; cotransfection with single-stranded DNA The Journal of biological chemistry High 9422773
1998 In nNOS-positive neurons of the neostriatum, neocortex, and hippocampus, the NMDAR1 subunit is present but specifically lacks the C1 splice cassette and preferentially contains the C2' terminus (generated when the C2 segment is absent), revealing that nNOS neurons express a distinct NMDAR1 isoform profile compared to surrounding neurons. Dual-label immunofluorescence with confocal microscopy using antibodies to nNOS and NMDAR1 cassettes (N1, C1, C2) in rat forebrain The Journal of neuroscience Medium 9464997
2013 The σ-1 receptor (Sig1R) binds directly and specifically to the GluN1 subunit within GluN1/GluN2A NMDA receptor heterotetramers, but not to GluN2A. This was shown by AFM imaging of subunit arrangement angles, co-isolation experiments, and in situ proximity ligation assays in intact cells. The Sig1R C-terminus faces extracellularly. Atomic force microscopy (AFM) imaging of receptor complexes; co-immunoprecipitation of Sig1R with GluN1 but not GluN2A; proximity ligation assay in intact cells The Journal of neuroscience High 24227730
2012 Functional GluN1/GluN2A NMDA receptors adopt an alternating 1/2/1/2 subunit arrangement (like subunits diagonal to one another). In this arrangement, GluN1 subunits occupy a 'proximal' position closer to the central pore axis than GluN2 subunits. Immature (intracellular) and mature (plasma-membrane-inserted) receptor pools can adopt different subunit arrangements. Electrophysiology (disulfide cross-linking between subunits combined with functional recording) and structural analysis based on AMPA receptor crystal structure homology PloS one High 22493736
2013 The GluN1 N-terminal domain (NTD) is neither static nor functionally silent. Perturbing GluN1 NTD conformation affects receptor gating and pharmacological properties. GluN1 NTD undergoes hinge-bending, twisting, and untwisting motions forming new intra- and intersubunit contacts, and acts in trans with GluN2 NTD to influence glutamate binding (but not GluN1 glycine binding). Single-molecule FRET, mutagenesis, electrophysiology of recombinant NMDARs; conformational perturbation of GluN1 NTD with designed mutations Nature structural & molecular biology High 23454977
2013 Crystal structures of the GluN1 ligand-binding domain (LBD) in the apo state reveal an open-cleft conformation. Computed free energy landscapes show GluN1 apo-state LBDs sample closed-cleft conformations via conformational selection (rather than induced-fit) for glycine binding, with a spectrum of hinge bending, rocking, twisting, and sweeping motions distinct from GluN2A and GluN3A LBDs. X-ray crystallography of GluN1 LBD; computational conformational free energy landscapes; principal component analysis Structure High 23972471
2013 Crystal structure of the GluN1 ligand-binding domain in complex with the competitive antagonist TK40 reveals that TK40 binds to the orthosteric glycine-binding site of GluN1 with an imino acetamido group acting as an α-amino acid bioisostere. Schild analysis confirmed competitive antagonism with Kb of 21–63 nM at GluN1/GluN2A-D, with >100-fold selectivity over GluN3-containing receptors. X-ray crystallography of GluN1 LBD–TK40 complex; Schild analysis; radioligand binding on rat brain membranes and purified GluN1 LBD; virtual screening The Journal of biological chemistry High 24072709
2012 The GluN1 exon 5-encoded N1 cassette in the amino-terminal domain is a key determinant of GluN1/GluN2D receptor function. GluN1-1b (exon 5-containing) receptors deactivate ~3-fold faster and have ~2-fold higher open probability than GluN1-1a receptors. Residue Lys211 in GluN1-1b is identified as a critical determinant of exon 5 control of deactivation and glutamate potency. Whole-cell and single-channel electrophysiology of recombinant GluN1/GluN2D receptors with GluN1 splice variants; site-directed mutagenesis; kinetic modeling The Journal of physiology High 22641781
2011 Intrasubunit disulfide bonds that constrain the M3-S2 linker in either the GluN1 or GluN2A subunit equally impair NMDA receptor pore opening, demonstrating that conformational freedom of the LBD-TMD linkers in both subunits is required and that the pore-opening mechanism involves tightly coupled intrasubunit dynamics at LBD-TMD linkers across all four subunits. Disulfide bond engineering (intrasubunit bonds between M3-S2 and S2-M4 linkers) in GluN1 or GluN2A; whole-cell and single-channel electrophysiology The Journal of general physiology High 21746848
2015 The GluN1 ligand-binding domain exists in multiple conformations even when glycine is bound, transitioning reversibly among states corresponding to different cleft widths on long timescales (much longer than channel opening). The LBD proceeds primarily from one adjacent smFRET state to the next, consistent with a sequential cleft-opening/closing mechanism. Single-molecule FRET on purified GluN1 LBD with glycine bound; step-transition and state-identification algorithm; denaturant shift experiments Biophysical journal High 26153703
2014 Concurrent stimulation of D1 dopamine receptors (D1R) and NMDA receptors drives formation of D1R/GluN1 complexes. Preventing D1R/GluN1 association with a cell-permeable TAT-GluN1C1 peptide leaves individual D1R and NMDAR signaling intact but blocks D1R-mediated facilitation of NMDAR calcium influx and ERK activation. D1R/GluN1 complexes control D1R-dependent enhancement of NMDAR currents and LTP in D1R-MSN, and are required for cocaine behavioral sensitization. Co-immunoprecipitation of endogenous D1R and GluN1; cell-permeable blocking peptide (TAT-GluN1C1); calcium imaging; ERK phosphorylation assay; whole-cell electrophysiology in striatal slices; in vivo behavioral sensitization Molecular psychiatry High 25070539
2018 Neurofilament light (NFL) protein interacts with GluN1 (NMDAR1) at synapses. NFL knockout reduces dendritic spines and GluN1 protein levels, elevates ubiquitin-dependent turnover of GluN1, increases hippocampal glutamate (by MRS), and depresses LTP. NFL+/- mice (at levels matching schizophrenia) show milder but similar NMDAR-related synaptic and behavioral deficits, indicating NFL stabilizes GluN1 at synapses. Co-immunoprecipitation of NFL and GluN1; NFL knockout and heterozygous mouse models; immunofluorescence; MRS; electrophysiology (LTP); behavioral tests Translational psychiatry High 30143609
2014 Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors have glutamate deactivation kinetics and pharmacological sensitivity to subunit-selective antagonists (ifenprodil, CP-101,606, TCN-201) and Zn2+ that are distinct from diheteromeric GluN1/GluN2A and GluN1/GluN2B receptors. The ifenprodil binding site geometry differs in triheteromers compared to GluN1/GluN2B diheteromers. Selective cell-surface expression of recombinant triheteromeric receptors using a dominant-negative subunit strategy; whole-cell voltage-clamp electrophysiology; pharmacological characterization Neuron High 24607230
2019 GluN1/GluN3A receptors are functionally expressed in adult mouse medial habenula neurons and are activated by glycine alone (not glutamate). Glial cells tune neuronal activity via GluN1/GluN3A receptors; reducing GluN1/GluN3A levels in the MHb prevented place-aversion conditioning, demonstrating a role for these glycine-gated NMDAR subtype in control of aversive behavior. Electrophysiology in adult mouse brain slices with CGP-78608 to unmask GluN1/GluN3A currents; viral knockdown in medial habenula; conditioned place aversion behavioral test Science High 31601771
2018 GluN1/GluN3A receptors can be unmasked by CGP-78608 (which blocks GluN1 glycine site to prevent desensitization) and modulated by an endogenous GluN3A disulfide bond that controls redox sensitivity, agonist sensitivity, and gating kinetics. Under reducing conditions, ambient glycine is sufficient to tonically activate GluN1/GluN3A receptors in hippocampal neurons. Whole-cell voltage-clamp electrophysiology in HEK cells and hippocampal slices; redox manipulation; pharmacology with CGP-78608 Nature communications High 30425244
2019 GluN1 alternative splicing controls nonionotropic (metabotropic) signaling by NMDARs. Glycine priming (binding to GluN1 glycine site without channel opening) induces receptor internalization only in GluN1 isoforms lacking the N1 cassette (exon 5); N1-containing isoforms block this nonionotropic signaling. C-terminal cassettes (C1, C2, C2') each permit glycine signaling. This was confirmed in CA1 pyramidal neurons (glycine priming present) vs. interneurons (glycine priming absent due to N1 expression). Recombinant receptor electrophysiology; engineered mouse knockin lines (GluN1 obligatorily containing or lacking N1 cassette); NMDAR internalization assays; electrophysiology in hippocampal CA1 pyramidal neurons and interneurons Proceedings of the National Academy of Sciences High 34187890
2019 GluN1 exon 5 (N1 cassette) inclusion/exclusion controls LTP magnitude and spatial memory performance. Mice lacking the N1 cassette (GluN1a) show significantly enhanced hippocampal LTP and faster learning with better spatial memory compared to mice obligatorily expressing exon 5 (GluN1b), despite no differences in basal synaptic transmission. Generation of GluN1a (exon 5 knockout) and GluN1b (obligatory exon 5 expression) knockin mice; hippocampal slice LTP recordings; Morris water maze; novel object recognition behavioral tests Cell reports High 31875540
2021 Cryo-EM structures of human GluN1-GluN2A NMDA receptor at ~4 Å reveal: competitive antagonists bound at GluN1 and GluN2A LBDs; a positive allosteric modulator shortens the distance between LBDs and TMD, stretching the gate open; the 'foot-in-the-door' blocker 9-aminoacridine binds within the LBD-TMD linker region (not the conventional TMD vestibule), providing molecular insights into crosstalk between LBDs and TMD during activation, inhibition, and allosteric transitions. Cryo-electron microscopy of full-length human GluN1-GluN2A NMDA receptor in complex with distinct ligands/modulators Neuron High 34186027
2022 Cryo-EM structures of human GluN1-GluN2C and GluN1-GluN2D NMDARs reveal unique inter-subunit and domain arrangements of GluN2C NMDARs, distinct from GluN2D. The GluN2C PAM (PYD-106) binding pocket is defined by these unique arrangements. Triheteromeric GluN1-2A-2C structure is also resolved. Single-particle cryo-electron microscopy of agonist-bound human GluN1-GluN2C, GluN1-GluN2A-GluN2C (triheteromeric), and GluN1-GluN2D receptors Molecular cell High 36309015
2024 Cryo-EM structures of GluN1/GluN3A NMDA receptors bound to antagonist (CNQX) and agonist (glycine) reveal a 1-3-1-3 heterotetrameric subunit arrangement. Glycine binding induces an unprecedented orientation shift in GluN3A subunits. Site-directed disruption of the unique glycine-bound subunit interface mitigates desensitization, establishing a structural basis for GluN3A-specific desensitization. Cryo-electron microscopy of GluN1/GluN3A NMDA receptors in agonist- and antagonist-bound states; site-directed mutagenesis of subunit interface with functional electrophysiology Science advances High 38598639
2013 Specificity protein 4 (Sp4) functionally regulates transcription of GluN1, GluN2A, and GluN2B NMDA receptor subunit genes, operating complementarily and in parallel with NRF-1 and NRF-2. Sp1 and Sp3 do not regulate these subunits. Sp4 operates in a complementary and concurrent manner with NRF-1/NRF-2 to couple energy metabolism with neuronal activity at the transcriptional level. Promoter-reporter assays; ChIP; EMSA; siRNA knockdown; transfection in neurons and non-neuronal cells Biochimica et biophysica acta Medium 23871830
2014 Sp4 transcription factor activates transcription of Nwk2 (Nervous Wreck 2/Fchsd1), which in turn mediates Sp4-dependent regulation of cell surface expression of GluN1 (NR1) and dendrite patterning. Acute Sp4 depletion reduces surface but not total NR1; this is rescued by Nwk2 expression. Identifies a Sp4-Nwk2-NR1 pathway regulating NMDAR trafficking and neuronal morphogenesis. Promoter-luciferase reporter assays; siRNA knockdown of Sp4 and Nwk2 in cerebellar granule neurons; rescue experiments; surface vs. total NR1 quantification by immunostaining; dendrite morphology analysis Developmental neurobiology Medium 25045015
2023 KCTD13 (a substrate adaptor for Cullin3-E3 ubiquitin ligase) facilitates lysine-48-linked polyubiquitination of GluN1 at lysine 860, targeting it for degradation via the ubiquitin-proteasome pathway. KCTD13 knockdown in hippocampus reduces surface glutamate receptor expression, impairs glutamate synaptic transmission, and enhances seizure susceptibility; overexpression has the opposite effect. Co-immunoprecipitation to identify GluN1 as KCTD13 substrate; ubiquitination assay specifying K48-linkage; site-directed mutagenesis to identify K860 ubiquitination site; hippocampal knockdown/overexpression by viral vectors; electrophysiology; seizure susceptibility assays in TLE mouse model Cell death and differentiation High 37142655
2016 De novo GRIN1 mutations clustering in transmembrane segments cause loss of NMDA receptor channel function with a dominant-negative effect (heterozygous mutations in transmembrane domains). Homozygous GRIN1 mutations (missense and truncation) also cause severe neurodevelopmental phenotypes. Functional characterization in Xenopus oocytes confirmed loss of channel function of varying severity. Two-electrode voltage-clamp in Xenopus oocytes expressing mutant GluN1 subunits; structural mapping of mutations onto 3D models; clinical genetics Neurology Medium 27164704
2017 The de novo GluN1-G620R mutation causes ~2-fold decrease in glutamate and glycine potency, strong decrease in Mg2+ block sensitivity, and significant reduction of current responses; GluN1-G620R/GluN2B complexes show significantly reduced delivery to the cell surface. This combination of trafficking defect and functional loss-of-function underlies the patient's neurodevelopmental phenotype. Electrophysiology (whole-cell patch-clamp) of GluN1-G620R/GluN2A and GluN1-G620R/GluN2B in HEK cells; surface trafficking assay (cell-surface biotinylation/immunofluorescence) Journal of human genetics High 28228639
2021 The recurrent de novo GluN1-M641I variant causes enhanced agonist potency and reduced Mg2+ block of NMDARs. These gain-of-function properties confer increased sensitivity to NMDAR channel blockers memantine, ketamine, and dextromethorphan compared to wild-type. Addition of memantine to the patient's treatment significantly reduced seizure burden. Two-electrode voltage-clamp in Xenopus oocytes and whole-cell recording in HEK cells; beta-lactamase reporter assay for surface expression; FDA-approved drug screening Annals of clinical and translational neurology High 34227748
2018 GRIN1 mutations associated with polymicrogyria (clustering in the S2 ligand-binding domain region and adjacent M3 helix) significantly alter receptor activity in vitro. Three mutations increased agonist potency while one reduced proton inhibition—a gain-of-function profile distinct from loss-of-function seen in previous GRIN1 mutations. Two-electrode voltage-clamp and whole-cell voltage-clamp electrophysiology of mutant GluN1-containing receptors in Xenopus oocytes and transfected cells; whole-exome sequencing Brain High 29365063
2020 Protocadherin 7 (PCDH7) interacts with the N-terminal domain of GluN1 (identified by unbiased screen of ~1,500 transmembrane proteins using purified GluN1-NTD bait). PCDH7 overexpression reduces synaptic NMDAR currents and induces dendritic structural changes; PCDH7 knockdown has opposing effects on dendritic morphology. Protein interaction screen using purified GluN1-NTD as bait against ~1,500 transmembrane proteins; primary neuron overexpression and knockdown; whole-cell electrophysiology; dendritic morphology analysis Scientific reports Medium 32616769
2019 Structural features of the glycine-binding site in GluN1 (and GluN3A) correlate with forward trafficking of NMDARs to the cell surface. Mutations in the GluN1 glycine-binding site alter surface delivery in both cell lines and primary hippocampal neurons, establishing that the glycine-binding site structure regulates receptor trafficking beyond just ligand binding. Site-directed mutagenesis of glycine-binding site residues; immunofluorescence and flow cytometry-based surface expression assays in HEK cells and primary rat hippocampal neurons Scientific reports Medium 31444392
2022 The pathogenic GluN1-N650K variant increases surface expression of GluN1/GluN2A and GluN1/GluN2B receptors (but not GluN1/GluN3A), enhances agonist potency, decreases conductance and open probability, and alters sensitivity to channel blockers memantine and ketamine. The K650 residue is located in the pore region; GluN1-N650K/GluN2B does not form functional receptors. Microscopy-based surface expression assays in HEK cells and hippocampal neurons; whole-cell patch-clamp electrophysiology; pharmacological profiling; excitotoxicity assays Neuropharmacology High 36341805
2014 In mice with selective Grin1 deletion in CRF neurons (especially in the CeA), fear memory acquisition and retention are enhanced without affecting fear extinction, exploration, or pain sensitivity. Amygdala Gria1 and Creb1 were elevated after fear conditioning in mutants, linking NMDAR function in CRF-CeA neurons to fear memory circuitry via AMPAR and CREB pathways. CRF-Cre × floxed Grin1 mice; CeA-targeted lentiviral Cre delivery; fear conditioning; RT-PCR for Gria1 and Creb1 PloS one Medium 25340785
2022 Platelet lineage-specific knockout of Grin1 (Pf4-Grin1-/- mice) causes defects in megakaryopoiesis, thrombopoiesis, and platelet function: reduced platelet counts, impaired platelet activation and spreading, reduced Ca2+ responses, and prolonged bleeding time. GluN1 deletion impairs F-actin and α-tubulin reorganization in megakaryocytes and reduces proplatelet formation, indicating NMDAR regulates PPF through MK-ECM interaction and cytoskeletal reorganization. Cre-loxP platelet lineage-specific Grin1 knockout; platelet function assays; calcium imaging; actin/tubulin immunofluorescence; colony and proplatelet formation assays; tail bleeding time; immune thrombocytopenia model Blood High 35245376
2017 Anti-GluN1-S2 antibody (targeting the glycine-binding region of GluN1) inhibits human platelet activation, aggregation, and thrombus formation. The antibody epitope maps to α-helix H within the GluN1 glycine-binding clamshell; computational modeling predicts antibody binding impairs channel opening. This establishes GluN1 glycine-binding site function in platelet NMDARs that regulate thrombus formation. Platelet aggregation assays; thrombus formation under flow; epitope mapping by mutagenesis; crystal structure-based computational modeling; rat vaccination model Platelets Medium 28277064
2024 Transcription factor TFAP2A positively regulates Grin1 gene expression, as confirmed by dual-luciferase reporter assay. In satellite glial cells of the DRG, Tfap2a knockdown reduces Grin1 expression; Grin1 knockdown in DRG alleviates neuropathic pain. Tfap2a siRNA also reduces NMDA-induced proinflammatory cytokine upregulation in primary SGCs. Dual-luciferase reporter assay for TFAP2A regulation of Grin1 promoter; siRNA knockdown in vivo (intrathecal) and in primary SGCs; RT-PCR and immunostaining; pain behavioral tests Biochemical pharmacology Medium 39009095
2018 Properties of triheteromeric GluN1/GluN1-1a/GluN1-1b/GluN2A and GluN1-1a/GluN1-1b/GluN2B receptors are intermediate between diheteromeric GluN1-1a/GluN1-1a/GluN2 and GluN1-1b/GluN1-1b/GluN2 receptors. A single copy of GluN3 pore residues strongly attenuates Mg2+ block and Ca2+ permeability; GluN1 and GluN2 pore residues contribute asymmetrically to Mg2+ block. FRET and FLIM to confirm triheteromeric assembly; selective surface expression strategy; whole-cell electrophysiology; pharmacological characterization; site-directed mutagenesis of pore residues Molecular pharmacology High 29483146
2014 GluN2 subunit is most likely directly responsible for the NMDA channel activation gate, while GluN1 assumes a role of more global control over gating conformational changes in GluN2. Specific mutations in the A7 residue of the SYTANLAAF motif in GluN1 (but not GluN2) result in channels with markedly enhanced affinity for both glycine and NMDA and can be activated by NMDA alone, suggesting GluN1 globally regulates GluN2 gating via this intersubunit interaction. Whole-cell patch-clamp electrophysiology; site-directed mutagenesis of SYTANLAAF motif A7 residue in GluN1 and GluN2; kinetic analysis of binding and unbinding rates Pflugers Archiv Medium 25339225
1995 The human GRIN1 gene is composed of 21 exons distributed over ~31 kb on chromosome 9q34.3-qter. Exons 4, 20, and 21 are subject to alternative splicing (identical in sequence to rat alternatively spliced exons), indicating all eight NMDAR1 isoforms found in rat are also expressed in human brain. The promoter contains two copies of the even-skipped homeodomain recognition sequence, implicating homeobox protein control of developmental expression. Cosmid cloning and sequencing of human GRIN1 gene; FISH mapping to chromosome 9q34.3-qter; computer analysis of pre-mRNA secondary structure and promoter elements Gene Medium 7622053
2016 Protons (extracellular acidification) potentiate GluN1/GluN3A receptor currents with half-maximal effect in the physiological pH range by slowing desensitization and accelerating recovery from desensitization. This modulation is mediated by residues at the heterodimer interface of the ligand-binding domain (GluN1 LBD interface with GluN3A). Whole-cell voltage-clamp of recombinant GluN1/GluN3A in HEK cells; site-directed mutagenesis of LBD interface residues; rapid solution exchange Scientific reports Medium 27000430
2017 GluN1 C-terminal alternatively spliced cassettes control steady-state activity level and pharmacological sensitivity (to zinc and protons) of GluN1/GluN3A receptors. Phosphorylation status of sites specific to certain GluN1 variants also modulates GluN1/GluN3A channel activity, indicating C-terminal domain splicing confers cell-specific and activity-dependent regulation. Whole-cell electrophysiology of recombinant GluN1 splice variants assembled with GluN3A in HEK293 cells; pharmacological characterization; phosphorylation state manipulation Neuropharmacology Medium 28365212
2023 The GluN1(Y668H) variant (associated with neurodevelopmental disorder) severely impairs surface expression of GluN1/GluN2A receptors, enhances sensitivity to glycine and glutamate by an order of magnitude, impairs Mg2+ block, reduces blocker (memantine/ketamine/MK-801) potency, and allows activation by either agonist alone. Single-channel recordings show this variant opens to multiple conductance levels more frequently than wild-type, revealing Y668 as a critical locus coupling receptor gating to ion channel conductance. Whole-cell and single-channel patch-clamp electrophysiology in HEK293 cells; surface expression assay; pharmacological profiling; primary hippocampal neuron recordings Epilepsia High 37734923
2020 EU1180-438, a negative allosteric modulator selective for GluN1/GluN3 receptors over GluN1/GluN2 NMDARs, inhibits GluN1/GluN3A currents in a voltage-independent, glycine concentration-independent manner. Site-directed mutagenesis identifies structural determinants of EU1180-438 activity near a short pre-M1 helix of GluN3 subunits. Non-stationary fluctuation analysis estimates native GluN1/GluN3A channel conductance at ~6.1 pS. Whole-cell electrophysiology of recombinant GluN1/GluN3 and GluN1/GluN2 receptors in HEK cells; native hippocampal CA1 neuron recordings; site-directed mutagenesis; non-stationary fluctuation analysis Neuropharmacology High 32389749
2024 α2δ-1 (a voltage-gated calcium channel regulatory subunit) interacts with NMDAR1 to form a complex that regulates NMDAR expression in the hypothalamus. Co-immunoprecipitation confirmed α2δ-1/NMDAR1 interaction. In α2δ-1 gene-knockout PC12 cells, quercetin had no effect on NMDAR1 expression, demonstrating the functional dependence of NMDAR1 regulation on α2δ-1. Co-immunoprecipitation; Western blot; immunofluorescence; α2δ-1 gene knockout in PC12 cells with NMDAR1 expression measurement; CUMS rat model CNS neuroscience & therapeutics Medium 38615365

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody. The Journal of neuroscience : the official journal of the Society for Neuroscience 802 8301357
1996 Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. The Journal of neuroscience : the official journal of the Society for Neuroscience 372 8613793
1996 Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 317 8824322
2014 Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors. Neuron 260 24607230
2016 Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy. Neurology 147 27164704
1998 Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of "neuroleptic-free" schizophrenics: evidence on reversible up-regulation by typical neuroleptics. Journal of neurochemistry 145 9832144
1993 Expression of endogenous NMDAR1 transcripts without receptor protein suggests post-transcriptional control in PC12 cells. The Journal of biological chemistry 145 8226739
1997 Differential subcellular regulation of NMDAR1 protein and mRNA in dendrites of dentate gyrus granule cells after perforant path transection. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 9045729
2003 Evidence that the N-methyl-D-aspartate subunit 1 receptor gene (GRIN1) confers susceptibility to bipolar disorder. Molecular psychiatry 90 12610658
2005 An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray. European journal of human genetics : EJHG 86 15841096
2013 The σ-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor. The Journal of neuroscience : the official journal of the Society for Neuroscience 84 24227730
2019 Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula. Science (New York, N.Y.) 83 31601771
2018 Unmasking GluN1/GluN3A excitatory glycine NMDA receptors. Nature communications 83 30425244
2013 Conformational analysis of NMDA receptor GluN1, GluN2, and GluN3 ligand-binding domains reveals subtype-specific characteristics. Structure (London, England : 1993) 83 23972471
2018 De novo mutations in GRIN1 cause extensive bilateral polymicrogyria. Brain : a journal of neurology 78 29365063
2015 GRIN1 mutations cause encephalopathy with infantile-onset epilepsy, and hyperkinetic and stereotyped movement disorders. Epilepsia 74 25864721
2017 GRIN1 mutation associated with intellectual disability alters NMDA receptor trafficking and function. Journal of human genetics 68 28228639
2002 Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys. Brain research 67 11844485
2014 D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses. Molecular psychiatry 65 25070539
1998 NMDAR1 glutamate receptor subunit isoforms in neostriatal, neocortical, and hippocampal nitric oxide synthase neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 9464997
2013 Allosteric signaling and dynamics of the clamshell-like NMDA receptor GluN1 N-terminal domain. Nature structural & molecular biology 61 23454977
2019 Functional and pharmacological properties of triheteromeric GluN1/2B/2D NMDA receptors. The Journal of physiology 59 31541561
2021 Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors. Neuron 57 34186027
2012 GluN1 splice variant control of GluN1/GluN2D NMDA receptors. The Journal of physiology 56 22641781
2017 The GluN1/GluN2B NMDA receptor and metabotropic glutamate receptor 1 negative allosteric modulator has enhanced neuroprotection in a rat subarachnoid hemorrhage model. Experimental neurology 52 29258835
1998 Single-stranded DNA-binding proteins and neuron-restrictive silencer factor participate in cell-specific transcriptional control of the NMDAR1 gene. The Journal of biological chemistry 50 9422773
2018 Neurofilament light interaction with GluN1 modulates neurotransmission and schizophrenia-associated behaviors. Translational psychiatry 47 30143609
2021 Anti-NMDAR encephalitis induced in mice by active immunization with a peptide from the amino-terminal domain of the GluN1 subunit. Journal of neuroinflammation 45 33612107
2019 Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1. Cell reports 45 31875540
2017 GluN1 and GluN2A NMDA Receptor Subunits Increase in the Hippocampus during Memory Consolidation in the Rat. Frontiers in behavioral neuroscience 45 28133447
2022 Structural insights into assembly and function of GluN1-2C, GluN1-2A-2C, and GluN1-2D NMDARs. Molecular cell 42 36309015
2010 Expression of the hippocampal NMDA receptor GluN1 subunit and its splicing isoforms in schizophrenia: postmortem study. Neurochemical research 40 20204507
2023 Excitatory GluN1/GluN3A glycine receptors (eGlyRs) in brain signaling. Trends in neurosciences 39 37248111
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
1993 Quantitation of NMDA receptor (NMDAR1) mRNA levels in the adult and developing rat CNS. Brain research. Molecular brain research 39 7689684
2011 Local constraints in either the GluN1 or GluN2 subunit equally impair NMDA receptor pore opening. The Journal of general physiology 36 21746848
2020 Negative allosteric modulation of GluN1/GluN3 NMDA receptors. Neuropharmacology 34 32389749
2019 Rett and Rett-like syndrome: Expanding the genetic spectrum to KIF1A and GRIN1 gene. Molecular genetics & genomic medicine 34 31512412
2013 A combinatorial approach of Proteomics and Systems Biology in unravelling the mechanisms of acute kidney injury (AKI): involvement of NMDA receptor GRIN1 in murine AKI. BMC systems biology 32 24172336
2007 Possible association between genetic variants at the GRIN1 gene and schizophrenia with lifetime history of depressive symptoms in a German sample. Psychiatric genetics 32 17728671
2018 Properties of Triheteromeric N-Methyl-d-Aspartate Receptors Containing Two Distinct GluN1 Isoforms. Molecular pharmacology 31 29483146
1997 Quantitative localization of NMDAR1 receptor subunit immunoreactivity in inferotemporal and prefrontal association cortices of monkey and human. Brain research 31 9138725
1995 Cloning and structure of the gene encoding the human N-methyl-D-aspartate receptor (NMDAR1). Gene 31 7622053
1995 Distribution of NMDAR1 receptor subunit mRNA and [125I]MK-801 binding in the hypothalamus of intact, castrate and castrate-DHTP treated male rats. Brain research. Molecular brain research 31 7707878
2024 Quercetin alleviates chronic unpredictable mild stress-induced depression-like behavior by inhibiting NMDAR1 with α2δ-1 in rats. CNS neuroscience & therapeutics 30 38615365
2021 Recurrent seizure-related GRIN1 variant: Molecular mechanism and targeted therapy. Annals of clinical and translational neurology 30 34227748
2012 An alternating GluN1-2-1-2 subunit arrangement in mature NMDA receptors. PloS one 30 22493736
1994 NMDA receptor (NMDAR1) expression in the rat hippocampus after forebrain ischemia. Neuroscience letters 30 8041510
2018 7-Methoxyderivative of tacrine is a 'foot-in-the-door' open-channel blocker of GluN1/GluN2 and GluN1/GluN3 NMDA receptors with neuroprotective activity in vivo. Neuropharmacology 28 30099049
2009 GRIN1 regulates micro-opioid receptor activities by tethering the receptor and G protein in the lipid raft. The Journal of biological chemistry 28 19861419
2004 Role of the metabotropic P2Y(4) receptor during hypoglycemia: cross talk with the ionotropic NMDAR1 receptor. Experimental cell research 28 15383322
2016 Protons Potentiate GluN1/GluN3A Currents by Attenuating Their Desensitisation. Scientific reports 27 27000430
2010 Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case-control study. Neuroscience letters 27 20438806
2024 Disease-Associated Variants in GRIN1, GRIN2A and GRIN2B genes: Insights into NMDA Receptor Structure, Function, and Pathophysiology. Physiological research 26 38836461
2019 Structural features in the glycine-binding sites of the GluN1 and GluN3A subunits regulate the surface delivery of NMDA receptors. Scientific reports 26 31444392
2017 Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells. Journal of Korean Neurosurgical Society 26 28264232
2014 Grin1 receptor deletion within CRF neurons enhances fear memory. PloS one 26 25340785
2013 ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response. BMC research notes 26 23688147
2013 Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B. Biochimica et biophysica acta 26 23871830
2013 Crystal structure and pharmacological characterization of a novel N-methyl-D-aspartate (NMDA) receptor antagonist at the GluN1 glycine binding site. The Journal of biological chemistry 26 24072709
2000 Mutation analysis of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia. Neuroscience letters 26 11109007
1999 Expression of glutamate receptor subunit/subtype messenger RNAS for NMDAR1, GLuR1, GLuR2 and mGLuR5 by accumbal projection neurons. Brain research. Molecular brain research 26 9878792
2024 Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel. Science advances 25 38598639
2020 PCDH7 interacts with GluN1 and regulates dendritic spine morphology and synaptic function. Scientific reports 25 32616769
2019 Ligustrazine suppresses renal NMDAR1 and caspase-3 expressions in a mouse model of sepsis-associated acute kidney injury. Molecular and cellular biochemistry 25 31732832
2010 Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis. The European journal of neuroscience 25 20345915
2008 Association between the G1001C polymorphism in the GRIN1 gene promoter and schizophrenia in the Iranian population. Journal of molecular neuroscience : MN 25 18792810
2004 Identification and biochemical analysis of GRIN1 and GRIN2. Methods in enzymology 25 15488195
2023 KCTD13-mediated ubiquitination and degradation of GluN1 regulates excitatory synaptic transmission and seizure susceptibility. Cell death and differentiation 24 37142655
2011 Changes in expression of splice cassettes of NMDA receptor GluN1 subunits within the frontal lobe and memory in mice during aging. Behavioural brain research 24 21443909
2012 Preweaning sensorimotor deficits and adolescent hypersociability in Grin1 knockdown mice. Developmental neuroscience 23 22571986
2015 Grin1 deletion in CRF neurons sex-dependently enhances fear, sociability, and social stress responsivity. Psychoneuroendocrinology 22 25938741
2015 Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via single-molecule FRET. Biophysical journal 22 26153703
2014 Dietary magnesium restriction reduces amygdala-hypothalamic GluN1 receptor complex levels in mice. Brain structure & function 22 24807818
2021 NMDAR1-Src-Pannexin1 Signal Pathway in the Trigeminal Ganglion Contributed to Orofacial Ectopic Pain Following Inferior Alveolar Nerve Transection. Neuroscience 21 33965504
2019 Progressive neuroanatomical changes caused by Grin1 loss-of-function mutation. Neurobiology of disease 21 31299220
2014 Transcription factor Sp4 regulates expression of nervous wreck 2 to control NMDAR1 levels and dendrite patterning. Developmental neurobiology 21 25045015
2003 N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) in schizophrenia: TDT and case-control analyses. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 21 12707933
2022 Deletion of Grin1 in mouse megakaryocytes reveals NMDA receptor role in platelet function and proplatelet formation. Blood 20 35245376
2012 Reducing expression of GluN1(0XX) subunit splice variants of the NMDA receptor interferes with spatial reference memory. Behavioural brain research 20 22360858
1998 [3H]MK-801 binding and the mRNA for the NMDAR1 subunit of the NMDA receptor are differentially distributed in human and rat forebrain. Brain research. Molecular brain research 20 9526033
2017 Identification of AICP as a GluN2C-Selective N-Methyl-d-Aspartate Receptor Superagonist at the GluN1 Glycine Site. Molecular pharmacology 19 28588066
2008 Dynamic expression patterns of G protein-regulated inducer of neurite outgrowth 1 (GRIN1) and its colocalization with Galphao implicate significant roles of Galphao-GRIN1 signaling in nervous system. Developmental dynamics : an official publication of the American Association of Anatomists 19 18729205
2022 Identification of a Subtype-Selective Allosteric Inhibitor of GluN1/GluN3 NMDA Receptors. Frontiers in pharmacology 18 35754487
1994 Expression of NMDAR1-1a (N598Q)/NMDAR2A receptors results in decreased cell mortality. European journal of pharmacology 18 7909752
2013 Modal gating of GluN1/GluN2D NMDA receptors. Neuropharmacology 17 23578394
2024 TFAP2A is involved in neuropathic pain by regulating Grin1 expression in glial cells of the dorsal root ganglion. Biochemical pharmacology 16 39009095
2021 Alternative splicing of GluN1 gates glycine site-dependent nonionotropic signaling by NMDAR receptors. Proceedings of the National Academy of Sciences of the United States of America 16 34187890
2016 GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation. Neuropharmacology 16 27012890
2015 Spermidine and Ca(2+), but not Na(+), can permeate NMDA receptors consisting of GluN1 and GluN2A or GluN2B in the presence of Mg(2+). Biochemical and biophysical research communications 16 26086092
2017 Inhibition of NMDA receptor function with an anti-GluN1-S2 antibody impairs human platelet function and thrombosis. Platelets 15 28277064
2002 Systematic mutation analysis of the human glutamate receptor, ionotropic, N-methyl-D-aspartate 1 gene(GRIN1) in schizophrenic patients. Psychiatric genetics 15 12454527
2020 The association between eating behavior and polymorphisms in GRIN2B, GRIK3, GRIA1 and GRIN1 genes in people with type 2 diabetes mellitus. Molecular biology reports 14 32037472
2017 Age-Dependent, Subunit Specific Action of Hydrogen Sulfide on GluN1/2A and GluN1/2B NMDA Receptors. Frontiers in cellular neuroscience 14 29225568
2014 The differential contribution of GluN1 and GluN2 to the gating operation of the NMDA receptor channel. Pflugers Archiv : European journal of physiology 14 25339225
2022 The pathogenic N650K variant in the GluN1 subunit regulates the trafficking, conductance, and pharmacological properties of NMDA receptors. Neuropharmacology 13 36341805
2019 Lectins modulate the functional properties of GluN1/GluN3-containing NMDA receptors. Neuropharmacology 13 31202607
2000 NMDAR1 isoforms in the rat superior olivary complex and changes after unilateral cochlear ablation. Brain research. Molecular brain research 13 10837919
2023 GRIN1 variants associated with neurodevelopmental disorders reveal channel gating pathomechanisms. Epilepsia 12 37734923
2017 Residues in the GluN1 C-terminal domain control kinetics and pharmacology of GluN1/GluN3A N-methyl-d-aspartate receptors. Neuropharmacology 12 28365212

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