Affinage

GRID1

Glutamate receptor ionotropic, delta-1 · UniProt Q9ULK0

Audit flag: wrong gene
Length
1009 aa
Mass
112.1 kDa
Annotated
2026-04-28
96 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GluD1 (encoded by GRID1) is an ionotropic glutamate receptor family member that functions primarily as a trans-synaptic signaling scaffold, organizing both excitatory and inhibitory synapse development and plasticity through non-ionotropic mechanisms. Its N-terminal domain binds presynaptic neurexin–cerebellin complexes to regulate postsynaptic NMDA and AMPA receptor levels via conserved C-terminal cytoplasmic motifs, with minimal constructs lacking ionotropic architecture fully recapitulating this signaling (PMID:34135511); its ligand-binding domain binds D-serine and GABA—not glutamate—with GABA binding producing long-lasting enhancement of GABAergic synaptic currents (PMID:38060673, PMID:36128700), and D-serine competitively inhibiting the Cbln1–GluD1 interaction (PMID:39890638). GluD1 additionally couples to mGlu1 receptors to generate slow depolarizing currents in dopamine neurons (PMID:28696429), carries a tonic cation conductance in serotonergic neurons (PMID:37154294), facilitates autophagic flux through C-terminal interactions with BECN1 and LAMP1 (PMID:41147487), and is required for normal dendritic spine pruning and the developmental GluN2B-to-GluN2A NMDAR subunit switch (PMID:25721396). Homozygous missense GRID1 variants (p.Thr752Met, p.Arg161His) cause intellectual disability and spastic paraplegia by impairing mGlu1/5 signaling and reducing dendrite complexity without disrupting GluD1 trafficking (PMID:38418578).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2011 Medium

    Establishing GluD1 as a synaptogenic molecule: it was unknown whether GluD1, like GluD2, could organize presynaptic differentiation; co-culture experiments showed GluD1's N-terminal domain induces both glutamatergic and GABAergic presynaptic differentiation in the presence of Cbln1, establishing GluD1 as a bona fide trans-synaptic organizer.

    Evidence HEK cell–neuron co-culture with exogenous Cbln1, GluD2-KO rescue

    PMID:22138648

    Open questions at the time
    • Single lab; no in vivo confirmation of GluD1 synaptogenic role at this stage
    • Endogenous cerebellin partner for GluD1 not identified
    • GABAergic versus glutamatergic synaptogenic specificity mechanism unclear
  2. 2014 High

    Demonstrating GluD1's requirement for synapse formation and cell survival in vivo: loss of GluD1 reduced parallel fiber–interneuron synapse density and interneuron number in cerebellum, establishing a non-redundant in vivo role for GluD1 in circuit connectivity and neuronal maintenance.

    Evidence GluD1 KO mouse, quantitative synapse and cell-count assays in cerebellar cortex

    PMID:24872547

    Open questions at the time
    • Molecular mechanism linking GluD1 loss to interneuron death not defined
    • Whether GluD1 acts cell-autonomously in interneurons not tested
  3. 2015 High

    Revealing GluD1 as a regulator of spine pruning and NMDAR subunit maturation: GluD1 KO mice showed excess spines, elevated excitatory transmission, disrupted LIMK1–cofilin signaling, and failure of the GluN2B-to-GluN2A switch, linking GluD1 to cytoskeletal remodeling and glutamate receptor subunit composition.

    Evidence GluD1 KO mouse, spine counting, electrophysiology, biochemical pathway analysis, GluN2B inhibitor rescue in mPFC and hippocampus

    PMID:25721396

    Open questions at the time
    • Direct biochemical link between GluD1 and LIMK1–cofilin pathway not established
    • Whether spine phenotype is developmental or maintenance-related unclear
  4. 2017 High

    Identifying a metabotropic coupling mode: GluD1 was shown to couple to mGlu1 to produce slow depolarizing currents in dopamine neurons, revealing that GluD1 can function as an effector ion channel downstream of a metabotropic receptor, a novel signaling paradigm for iGluR family members.

    Evidence HEK cell co-expression, dominant-negative GluD1 mutant in slices, GRID1 KO mice, in vivo dopamine neuron recordings

    PMID:28696429

    Open questions at the time
    • Molecular mechanism of mGlu1–GluD1 coupling (direct interaction vs. intermediary) not resolved
    • Whether this coupling occurs outside midbrain dopamine neurons unknown
  5. 2019 High

    Defining GluD1 synaptic trafficking rules: phosphorylation of C-terminal T923 was shown to be critical for synaptic (but not surface) localization, independent of the PDZ-binding motif, revealing a trafficking mechanism distinct from AMPARs and establishing the C-terminal domain as a regulatory hub.

    Evidence Chimeric GluD1/GluK1 constructs, site-directed mutagenesis, neuronal imaging and electrophysiology

    PMID:30824864

    Open questions at the time
    • Kinase responsible for T923 phosphorylation not identified
    • Activity-dependent regulation of this phosphorylation not tested
  6. 2019 Medium

    Demonstrating GluD1–GluD2 hetero-association: co-immunoprecipitation from brain tissue and ultrastructural co-localization showed GluD1 and GluD2 form complexes at the same glutamatergic synapses, suggesting functional heteromeric assembly.

    Evidence Co-IP in HEK293T cells and brain lysates, SDS-digested freeze-fracture replica labeling in retrosplenial cortex

    PMID:31625608

    Open questions at the time
    • Stoichiometry and functional consequence of GluD1/GluD2 heteromers not determined
    • Whether heteromers have distinct signaling properties is untested
  7. 2020 High

    Resolving GluD1 architecture: cryo-EM revealed a unique non-swapped tetrameric arrangement at the ATD–LBD interface, distinguishing GluD receptors from all other iGluR families and providing a structural basis for their distinct signaling properties.

    Evidence Cryo-EM of rat GluD1 complexed with calcium and 7-chlorokynurenic acid

    PMID:31925409

    Open questions at the time
    • Full-length structure with transmembrane domain not resolved at this stage
    • Functional consequence of non-swapped architecture for signaling not directly tested
  8. 2021 High

    Establishing GluD1 as a non-ionotropic trans-synaptic signal transduction device: minimal constructs containing only the NTD and CTD joined by an unrelated transmembrane domain fully recapitulated neurexin–cerebellin-dependent NMDAR and AMPAR regulation, proving the mechanism bypasses ionotropic gating entirely.

    Evidence Minimal/chimeric constructs, electrophysiology, domain-swap and loss-of-function experiments in hippocampal synapses

    PMID:34135511

    Open questions at the time
    • Conformational change linking extracellular binding to cytoplasmic signaling not visualized
    • Identity of cytoplasmic effectors recruited by the C-terminal motifs not fully catalogued
  9. 2022 High

    Characterizing D-serine binding to GluD1-LBD: crystal structure and ITC revealed D-serine binds GluD1 with ~160 µM Kd (5-fold lower than GluD2), with Glu822 critical for activation and Pro725 affecting interlobe closure dynamics, establishing molecular determinants of GluD1 ligand recognition.

    Evidence X-ray crystallography at 2.57 Å, ITC, oocyte electrophysiology, molecular dynamics

    PMID:36128700

    Open questions at the time
    • Physiological source and concentration of D-serine at GluD1-expressing synapses not established
    • Whether D-serine binding triggers non-ionotropic signaling or primarily modulates trans-synaptic interactions unclear
  10. 2023 High

    Discovering GABA as a GluD1 ligand: GABA binding to the LBD was demonstrated biochemically and structurally, and shown to produce long-lasting enhancement of GABAergic synaptic currents in hippocampus via a non-ionotropic, trans-synaptically anchored mechanism—making GluD1 the first iGluR family member with a GABA-binding function.

    Evidence Binding assays, structural analysis of LBD, patch-clamp in hippocampal slices, loss-of-function

    PMID:38060673

    Open questions at the time
    • Whether GABA binding and D-serine binding are competitive at the same site not fully resolved
    • Downstream signaling cascade from GABA-bound GluD1 to GABAergic potentiation not identified
  11. 2023 Medium

    Identifying a tonic cation conductance: GluD1 carries a G-protein-independent, calcium-regulated tonic current in dorsal raphe serotonergic neurons that sets resting membrane potential, expanding GluD1's repertoire to include a constitutive ionotropic mode independent of classical ligand gating.

    Evidence Voltage-clamp and current-clamp in adult mouse brain slices, pharmacological GluD1 block

    PMID:37154294

    Open questions at the time
    • Molecular mechanism of calcium-dependent regulation of this tonic current not defined
    • Whether this tonic current occurs in other GluD1-expressing neuron types untested
  12. 2024 High

    Linking GRID1 mutations to human disease: homozygous GRID1 missense variants were shown to cause intellectual disability and spastic paraplegia by impairing mGlu1/5 signaling and reducing dendritic complexity without disrupting trafficking or cerebellin binding, establishing GRID1 as a Mendelian disease gene.

    Evidence Patient variant modeling, electrophysiology, Ca²⁺ and ERK pathway assays, neuronal morphology in dissociated and organotypic cultures

    PMID:38418578

    Open questions at the time
    • Genotype–phenotype correlation across additional GRID1 variants not yet established
    • Whether disease mechanism is primarily mGlu1/5-dependent or involves trans-synaptic signaling impairment not separated
  13. 2024 Medium

    Characterizing disease-associated channel variants: an ATD variant disrupted GluD1–Cbln2 complex formation while M3 domain variants created constitutively active channels, and pentamidine was identified as an inhibitor of pathogenic constitutive currents, beginning to define pharmacological rescue strategies.

    Evidence Electrophysiology, biochemical binding assays, pentamidine pharmacology

    PMID:37944084

    Open questions at the time
    • In vivo efficacy of pentamidine not tested
    • Whether constitutive channel activity is pathogenic in patient neurons not confirmed
  14. 2025 Medium

    Revealing D-serine as a competitive modulator of trans-synaptic assembly: D-serine concentration-dependently inhibits Cbln1–GluD1 interaction (IC50 ~300 µM) and blocks Cbln1-dependent synaptic and behavioral effects, establishing a ligand-dependent switch between trans-synaptic scaffolding and ligand-gated signaling modes.

    Evidence Cell-binding assay, ex vivo central amygdala slice electrophysiology, in vivo nociception assays

    PMID:39890638

    Open questions at the time
    • Physiological context where D-serine reaches effective concentrations at GluD1 synapses not demonstrated
    • Whether GABA similarly modulates Cbln1 binding not tested
  15. 2025 Medium

    Discovering a non-synaptic function in autophagy: GluD1 was found to interact with BECN1 and LAMP1 via its C-terminal domain (through nGOPC/nPIST) to promote autophagic flux; a GluD1-derived peptide rescued autophagy impairment and AMPAR upregulation in pain models, linking GluD1 to protein homeostasis beyond synaptic signaling.

    Evidence Co-IP of GluD1 with BECN1/LAMP1/nGOPC, Tat-HRSPN peptide in vivo, autophagy flux assays, CeA electrophysiology, pain behavioral models

    PMID:41147487

    Open questions at the time
    • Whether autophagy function is constitutive or activity-dependent not established
    • Structural basis of GluD1–BECN1 interaction not defined
    • Generalizability beyond central amygdala not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the conformational mechanism linking extracellular ligand/cerebellin binding to cytoplasmic effector recruitment; whether GluD1 heteromers with GluD2 have distinct signaling properties; the physiological conditions under which ionotropic versus non-ionotropic modes predominate; and the full catalogue of C-terminal effectors mediating NMDAR/AMPAR regulation and autophagic signaling.
  • No structure of full signaling complex (neurexin–Cbln–GluD1 with cytoplasmic partners)
  • Ionotropic vs. non-ionotropic mode selection mechanism unknown
  • Complete cytoplasmic interactome not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0005215 transporter activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-9612973 Autophagy 1
Partners
BECN1CBLN1CBLN2GOPCGRID2GRM1NRXN1NRXN3
Complex memberships
GluD1–GluD2 heteromeric complexneurexin–cerebellin–GluD1 trans-synaptic complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2021 GluD1 functions as a trans-synaptic signal transduction device rather than a classical ion channel: presynaptic neurexin-1–cerebellin-2 and neurexin-3–cerebellin-2 complexes bind postsynaptic GluD1 and differentially regulate NMDA and AMPA receptor levels through conserved cytoplasmic C-terminal motifs (5–13 residues). Minimal GluD1 constructs containing only the N-terminal cerebellin-binding domain and C-terminal cytoplasmic domain joined by an unrelated transmembrane region fully recapitulate NMDA and AMPA receptor regulation, demonstrating the mechanism bypasses ionotropic architecture. Chimeric/minimal-construct expression, electrophysiology, biochemical assays in hippocampal synapses; loss-of-function and domain-swap experiments Nature High 34135511
2023 GluD1 binds GABA (a previously unknown ligand for any iGluR family member) through its ligand-binding domain, and GluD1 activation produces long-lasting enhancement of GABAergic synaptic currents in adult mouse hippocampus via a non-ionotropic mechanism that requires trans-synaptic anchoring. Biochemical binding assays, X-ray/structural analysis of LBD, patch-clamp electrophysiology in hippocampal slices, loss-of-function experiments Science High 38060673
2020 Cryo-EM structures of rat GluD1 reveal a non-swapped architecture at the ATD–LBD interface, in contrast to all other iGluR families where dimer partners are swapped between layers, establishing unique principles of GluD receptor assembly. Cryo-EM structural determination of GluD1 complexed with calcium and 7-chlorokynurenic acid Nature Structural & Molecular Biology High 31925409
2017 GluD1 couples to metabotropic glutamate receptor mGlu1 to generate slow depolarizing currents in midbrain dopamine neurons; this current is abolished by a dominant-negative dead-pore GluD1 mutant and is absent in GRID1 knockout mice, demonstrating GluD1 is required for mGlu1-dependent slow synaptic transmission and burst firing of dopamine neurons. HEK cell co-expression electrophysiology, dominant-negative mutant expression in brain slices, GRID1 KO mice, in vivo dopamine neuron recordings Molecular Psychiatry High 28696429
2014 In the cerebellar cortex, GluD1 is expressed in molecular layer interneurons and concentrated at parallel fiber (PF) synapses on interneuron somata. In GluD1 knockout mice, the density of PF synapses on interneuron somata is significantly reduced and interneuron number/size is diminished, demonstrating GluD1 regulates PF–interneuron synapse connectivity and interneuron differentiation/survival. Histochemical localization, GluD1 knockout mouse analysis, quantitative synapse and cell-count assays Journal of Neuroscience High 24872547
2011 GluD1 expressed in non-neuronal HEK cells induces presynaptic differentiation of cerebellar granule neurons via its N-terminal domain; in the presence of Cbln1, GluD1 additionally induces both glutamatergic and GABAergic presynaptic differentiation in hippocampal co-cultures, and rescues synapse formation defects in GluD2-knockout Purkinje neurons. HEK cell–neuron co-culture assay, exogenous Cbln1 addition, GluD2-KO rescue experiment Biochemical and Biophysical Research Communications Medium 22138648
2015 GluD1 knockout mice exhibit higher dendritic spine number, greater excitatory neurotransmission, increased synapse number in mPFC and CA1 hippocampus, and abnormal LIMK1–cofilin signaling with a lower GluN2A/GluN2B ratio, establishing GluD1 as required for normal spine development and GluN2B-to-GluN2A NMDAR subunit switch. GluD1 KO mouse analysis, dendritic spine counting, electrophysiology, biochemical pathway analysis (LIMK1–cofilin), GluN2B inhibitor rescue Neuropharmacology High 25721396
2019 GluD1 synaptic trafficking depends on its C-terminal domain but not on the PDZ-binding motif; phosphorylation of threonine T923 in the C-terminal domain is critical for synaptic (but not surface) localization of GluD1, revealing a unique trafficking mechanism distinct from AMPARs. Chimeric GluD1/GluK1 constructs, mutagenesis of C-terminal domain and PDZ motif, electrophysiology and imaging in neurons Molecular Psychiatry High 30824864
2022 X-ray crystallography of the GluD1 ligand-binding domain (LBD) reveals its apo structure at 2.57 Å; D-serine binds GluD1-LBD with Kd ~160 µM (approximately 5-fold lower affinity than GluD2); Glu822 is identified as a critical determinant of receptor activation in GluD1 A654T; molecular dynamics indicate GluD1 apo structure is less flexible than GluD2 and Pro725 affects LBD interlobe closure. X-ray crystallography, isothermal titration calorimetry, electrophysiology in Xenopus oocytes, molecular dynamics simulation The FEBS Journal High 36128700
2019 GluD1 and GluD2 form a coimmunoprecipitable protein complex in HEK293T cells and in native cerebral cortex and hippocampus; both receptors are co-expressed on the same glutamatergic synapses in the retrosplenial cortex, as shown by SDS-digested freeze-fracture replica labeling. Co-immunoprecipitation in HEK293T cells and brain tissue, SDS-digested freeze-fracture replica labeling, quantitative immunoblotting with chimeric protein standards Journal of Comparative Neurology Medium 31625608
2024 Homozygous missense GRID1 variants (p.Thr752Met and p.Arg161His) cause intellectual disability and spastic paraplegia; mechanistically these mutations alter hinge/LBD function, impair mGlu1/5 receptor signaling via Ca2+ and ERK pathways, and reduce dendrite complexity and excitatory synapse density when expressed in neurons, without disrupting GluD1 trafficking or cerebellin binding. Molecular modeling, electrophysiological recordings, Ca2+ imaging, ERK pathway assays, neuronal morphology analysis in dissociated and organotypic cultures Molecular Psychiatry High 38418578
2024 A GRID1 variant in the distal amino-terminal domain (predicted to contact Cbln2/Cbln4) disrupts GluD1–Cbln2 complex formation in biochemical assays; other rare M3 domain variants (including GluD1-A650T analogous to the GluD2 lurcher mutation) create constitutively active channels; pentamidine potently inhibits constitutive currents of GluD receptor variants. Electrophysiological assays, biochemical complex formation assays, pharmacological inhibition with pentamidine Human Molecular Genetics Medium 37944084
2025 D-serine binds GluD1's ligand-binding domain and concentration-dependently inhibits the interaction between Cbln1 and GluD1 (IC50 ~300 µM) in a cell-binding assay; pre-treatment with D-serine blocks the pro-synaptic and nociceptive effects of recombinant Cbln1 in central amygdala slices and in vivo. In vitro cell-binding assay, ex vivo slice electrophysiology, in vivo behavioral (nociception) assays Cellular and Molecular Life Sciences Medium 39890638
2023 GluD1 carries a G-protein-independent tonic cation current in dorsal raphe nucleus neurons regulated by physiological levels of external calcium; block of GluD1 channels hyperpolarizes the membrane by ~7 mV, reducing neuronal excitability, and this tonic current is unaffected by D-serine or glycine supplementation. Voltage-clamp and current-clamp electrophysiology from adult mouse brain slices, pharmacological block of GluD1 EMBO Reports Medium 37154294
2025 GRID1/GluD1 directly facilitates autophagic flux in central amygdala neurons via interaction with autophagy mediators nGOPC/nPIST, BECN1, and LAMP1; a GluD1 C-terminal-derived peptide (Tat-HRSPN) promotes autophagy and reduces AMPA receptor expression; GRID1/CBLN1 downregulation during inflammatory and neuropathic pain impairs autophagic flux and increases AMPAR expression in CeA. Co-immunoprecipitation (GluD1 with BECN1/LAMP1/nGOPC), peptide (Tat-HRSPN) in vivo infusion, autophagy flux assays, electrophysiology in CeA slices, pain behavioral models Autophagy Medium 41147487
2020 In both mouse and monkey striatum, GluD1 immunoreactivity is localized by electron microscopy predominantly to dendritic shafts and glial processes, with synaptic and perisynaptic labeling at glutamatergic axo-dendritic and axo-spinous synapses; confocal microscopy shows preferential colocalization with thalamic (over cortical) terminals. Immunoelectron microscopy (including immunogold), confocal microscopy, ultrastructural subcellular localization Journal of Comparative Neurology Medium 33084025
2026 Cryo-EM structures of human GluD1 and single-channel bilayer recordings demonstrate that GABA or D-serine binding to the LBD enables cation influx through the hGluD1 ion channel; hGluD1 has a non-swapped architecture containing conserved iGluR moieties that enable ligand-gating. Cryo-EM structure determination, single-channel bilayer electrophysiology, ligand-binding functional assays bioRxiv (preprint)preprint Medium 41993446
2024 Grid1 knockdown in the hypothalamus decreases Grid1 and Rfrp-3 mRNA, increases Gnrh mRNA, advances vaginal opening (earlier puberty onset) and decreases progesterone levels in female rats, placing GluD1 in a pathway that regulates GnRH/RFRP-3 signaling and puberty onset. Lentiviral Grid1 knockdown in hypothalamic neurons, intracerebroventricular injection, RT-PCR gene expression, hormone ELISA, histology Journal of Veterinary Medical Science Low 38479882

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Characterization of a new rice glutelin gene GluD-1 expressed in the starchy endosperm. Journal of experimental botany 111 18980953
2014 Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 24872547
2000 Nerve tissue-specific (GLUD2) and housekeeping (GLUD1) human glutamate dehydrogenases are regulated by distinct allosteric mechanisms: implications for biologic function. Journal of neurochemistry 79 11032875
1999 Identification of alleles for complex gene loci Glu-A1, Glu-B1, and Glu-D1, which code for high molecular weight subunits of glutenin in Japanese hexaploid wheat varieties. Journal of agricultural and food chemistry 78 10606608
2009 Transgenic expression of Glud1 (glutamate dehydrogenase 1) in neurons: in vivo model of enhanced glutamate release, altered synaptic plasticity, and selective neuronal vulnerability. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 19890003
2009 Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations. European journal of endocrinology 70 19690084
2021 GluD1 is a signal transduction device disguised as an ionotropic receptor. Nature 69 34135511
2014 GluD1 is a common altered player in neuronal differentiation from both MECP2-mutated and CDKL5-mutated iPS cells. European journal of human genetics : EJHG 60 24916645
2009 Dissection of phenotype reveals possible association between schizophrenia and Glutamate Receptor Delta 1 (GRID1) gene promoter. Schizophrenia research 56 19346103
2015 Essential role of GluD1 in dendritic spine development and GluN2B to GluN2A NMDAR subunit switch in the cortex and hippocampus reveals ability of GluN2B inhibition in correcting hyperconnectivity. Neuropharmacology 55 25721396
2007 A case-control association study between the GRID1 gene and schizophrenia in the Chinese Northern Han population. Schizophrenia research 55 17490860
2012 Deletion of glutamate dehydrogenase 1 (Glud1) in the central nervous system affects glutamate handling without altering synaptic transmission. Journal of neurochemistry 48 22924626
2017 GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons. Molecular psychiatry 47 28696429
2009 Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and endoplasmic reticulum. Biochemistry and cell biology = Biochimie et biologie cellulaire 47 19448744
2011 Induction of excitatory and inhibitory presynaptic differentiation by GluD1. Biochemical and biophysical research communications 46 22138648
2020 GluD1 knockout mice with a pure C57BL/6N background show impaired fear memory, social interaction, and enhanced depressive-like behavior. PloS one 45 32078638
2002 Substitution of Ser for Arg-443 in the regulatory domain of human housekeeping (GLUD1) glutamate dehydrogenase virtually abolishes basal activity and markedly alters the activation of the enzyme by ADP and L-leucine. The Journal of biological chemistry 44 12324473
2020 Cryo-EM structures of the ionotropic glutamate receptor GluD1 reveal a non-swapped architecture. Nature structural & molecular biology 41 31925409
2018 Glutamate dehydrogenase (GLUD1) expression in breast cancer. Breast cancer research and treatment 39 30470977
2002 Unregulated elevation of glutamate dehydrogenase activity induces glutamine-stimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase. Diabetes 39 11872671
2019 Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. The Journal of comparative neurology 37 31625608
2023 GluD1 binds GABA and controls inhibitory plasticity. Science (New York, N.Y.) 34 38060673
2011 Neuronal Glud1 (glutamate dehydrogenase 1) over-expressing mice: increased glutamate formation and synaptic release, loss of synaptic activity, and adaptive changes in genomic expression. Neurochemistry international 33 21397652
2022 Oncogenic circTICRR suppresses autophagy via binding to HuR protein and stabilizing GLUD1 mRNA in cervical cancer. Cell death & disease 30 35595754
2012 Glutamate receptor δ 1 (GRID1) genetic variation and brain structure in schizophrenia. Journal of psychiatric research 30 23017809
2012 The complex regulation of human glud1 and glud2 glutamate dehydrogenases and its implications in nerve tissue biology. Neurochemistry international 27 22658952
2020 Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells Through Regulating GLUD1-P38 MAPK Signaling Pathway. OncoTargets and therapy 23 32801758
1993 Three human glutamate dehydrogenase genes (GLUD1, GLUDP2, and GLUDP3) are located on chromosome 10q, but are not closely physically linked. Genomics 22 8244384
2015 Expression of human GLUD1 and GLUD2 glutamate dehydrogenases in steroid producing tissues. Molecular and cellular endocrinology 21 26241911
1994 PCR analysis of genes encoding allelic variants of high-molecular-weight glutenin subunits at the Glu-D1 locus. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 20 24185923
2020 Hyperinsulinism associated with GLUD1 mutation: allosteric regulation and functional characterization of p.G446V glutamate dehydrogenase. Human genomics 19 32143698
2016 Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions. Neurochemical research 19 27422263
2013 Development of mice with brain-specific deletion of floxed glud1 (glutamate dehydrogenase 1) using cre recombinase driven by the nestin promoter. Neurochemical research 19 23595828
2024 GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis. Discover oncology 16 38216781
2022 GLUD1 suppresses renal tumorigenesis and development via inhibiting PI3K/Akt/mTOR pathway. Frontiers in oncology 15 36203437
2020 Ultrastructural localization of glutamate delta 1 (GluD1) receptor immunoreactivity in the mouse and monkey striatum. The Journal of comparative neurology 14 33084025
2014 Metabolism changes during aging in the hippocampus and striatum of glud1 (glutamate dehydrogenase 1) transgenic mice. Neurochemical research 14 24442550
2022 Differences between the GluD1 and GluD2 receptors revealed by GluD1 X-ray crystallography, binding studies and molecular dynamics. The FEBS journal 13 36128700
2003 DHPLC scoring of a SNP between promoter sequences of HMW glutenin x-type alleles at the Glu-D1 locus in wheat. Journal of agricultural and food chemistry 13 12848495
2024 Clinical features, functional consequences, and rescue pharmacology of missense GRID1 and GRID2 human variants. Human molecular genetics 12 37944084
2023 STUB1-mediated ubiquitination regulates the stability of GLUD1 in lung adenocarcinoma. iScience 12 37416474
2019 Mechanisms underlying the synaptic trafficking of the glutamate delta receptor GluD1. Molecular psychiatry 12 30824864
2014 Mutational analysis of ABCC8, KCNJ11, GLUD1, HNF4A and GCK genes in 30 Chinese patients with congenital hyperinsulinism. Endocrine journal 12 25008049
2013 Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat. PloS one 12 24098671
2020 miR‑30a‑5p inhibits hypoxia/reoxygenation‑induced oxidative stress and apoptosis in HK‑2 renal tubular epithelial cells by targeting glutamate dehydrogenase 1 (GLUD1). Oncology reports 11 32945480
2024 GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels. Developmental cell 10 39121856
2023 Potentiation of neuronal activity by tonic GluD1 current in brain slices. EMBO reports 10 37154294
2020 Absence of Dx2 at Glu-D1 Locus Weakens Gluten Quality Potentially Regulated by Expression of Nitrogen Metabolism Enzymes and Glutenin-Related Genes in Wheat. International journal of molecular sciences 10 32085665
2019 Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1. Indian journal of pediatrics 10 31119523
2024 GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses. Molecular psychiatry 9 38418578
2024 Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis. Journal of molecular cell biology 9 38587834
2024 Deacetylation of GLUD1 maintains the survival of lung adenocarcinoma cells under glucose starvation by inhibiting autophagic cell death. Cell insight 9 39144257
2022 Mosaic GLUD1 Mutations Associated with Hyperinsulinism Hyperammonemia Syndrome. Hormone research in paediatrics 9 35952631
2022 Identification of Glu-D1 Alleles and Novel Marker-Trait Associations for Flour Quality and Grain Yield Traits under Heat-Stress Environments in Wheat Lines Derived from Diverse Accessions of Aegilops tauschii. International journal of molecular sciences 9 36233335
2020 Hyperinsulinism hyperammonaemia (HI/HA) syndrome due to GLUD1 mutation: phenotypic variations ranging from late presentation to spontaneous resolution. Journal of pediatric endocrinology & metabolism : JPEM 9 32229669
2016 Hyperinsulinism-hyperammonemia syndrome: a de novo mutation of the GLUD1 gene in twins and a review of the literature. Journal of pediatric endocrinology & metabolism : JPEM 9 27383869
2020 Effects of Nitrogen Application in the Wheat Booting Stage on Glutenin Polymerization and Structural-Thermal Properties of Gluten with Variations in HMW-GS at the Glu-D1 Locus. Foods (Basel, Switzerland) 8 32197430
2011 Differential levels of glutamate dehydrogenase 1 (GLUD1) in Balb/c and C57BL/6 mice and the effects of overexpression of the Glud1 gene on glutamate release in striatum. ASN neuro 8 21446915
2002 The cytogenetics and molecular characteristics of a translocated chromosome 1AS.1AL-1DL with a Glu-D1 locus in durum wheat. Cellular & molecular biology letters 8 12378261
2001 A Japanese case of congenital hyperinsulinism with hyperammonemia due to a mutation in glutamate dehydrogenase (GLUD1) gene. Internal medicine (Tokyo, Japan) 8 11201367
2025 D-Serine disrupts Cbln1 and GluD1 interaction and affects Cbln1-dependent synaptic effects and nocifensive responses in the central amygdala. Cellular and molecular life sciences : CMLS 7 39890638
2016 2,3,7,8 Tetrachlorodibenzo-p-dioxin-induced RNA abundance changes identify Ackr3, Col18a1, Cyb5a and Glud1 as candidate mediators of toxicity. Archives of toxicology 6 27136898
2009 Development of isohomoeoallelic lines within the wheat cv. Courtot for high molecular weight glutenin subunits: transfer of the Glu-D1 locus to chromosome 1A. TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 6 19436987
2025 Nuclear PHGDH regulates macrophage polarization through transcriptional repression of GLUD1 and GLS2 in breast cancer. Cancer biology & medicine 5 40434360
2024 IDH2 and GLUD1 depletion arrests embryonic development through an H4K20me3 epigenetic barrier in porcine parthenogenetic embryos. Zoological research 5 39318125
2025 Novel histone deacetylase-5 inhibitor T2943 exerts an anti-depressive effect in mice by enhancing GRID1 expression. Scientific reports 4 39915556
2025 Trans-synaptic signaling through GRID1/glutamate receptor delta-1 and CBLN1/cerebellin-1 facilitates autophagic flux in central amygdala and prevents chronic pain. Autophagy 4 41147487
2024 Dynamic behaviors of protein and water associated with fresh noodle quality during processing based on different HMW-GSs at Glu-D1. Food chemistry 4 38754351
2023 Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1. Endocrine connections 4 35951311
2023 Polymorphism and expression of GLUD1 in relation to reproductive performance in Jining Grey goats. Archives animal breeding 4 38205377
2015 Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene. Journal of pediatric endocrinology & metabolism : JPEM 4 25781533
2011 Biochemical evaluation of an infant with hypoglycemia resulting from a novel de novo mutation of the GLUD1 gene and hyperinsulinism-hyperammonemia syndrome. Journal of pediatric endocrinology & metabolism : JPEM 4 21932603
2024 Grid1 regulates the onset of puberty in female rats. The Journal of veterinary medical science 3 38479882
2016 A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA). Journal of pediatric endocrinology & metabolism : JPEM 3 26656609
2016 A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. Journal of medical case reports 3 26839063
2025 A-485 alleviates postmenopausal osteoporosis by activating GLUD1 deacetylation through the SENP1-Sirt3 signal pathway. Journal of orthopaedic surgery and research 2 40442713
2023 UBE3A and transsynaptic complex NRXN1-CBLN1-GluD1 in a hypothalamic VMHvl-arcuate feedback circuit regulates aggression. bioRxiv : the preprint server for biology 2 36909588
2021 Diazoxide-Induced Neutropenia and Long-Term Follow-up in a Patient with Hyperinsulinemia-Hyperammonemia due to GLUD1 Mutation. Acta endocrinologica (Bucharest, Romania : 2005) 2 35342475
2017 [Effect of GLUD1 on proliferation, osteogenic differentiation and mineralization of human dental pulp stem cells]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 2 29199326
2024 Energy metabolism-related GLUD1 contributes to favorable clinical outcomes of IDH-mutant glioma. BMC neurology 1 39272024
2023 Increases in anterograde axoplasmic transport in neurons of the hyper-glutamatergic, glutamate dehydrogenase 1 (Glud1) transgenic mouse: Effects of glutamate receptors on transport. Journal of neurochemistry 1 38124277
2013 [ABCC8, KCNJ11 and GLUD1 gene mutation analysis in congenital hyperinsulinism pedigree]. Zhonghua yi xue za zhi 1 23902843
2026 CBLN1 inhibits the inflammatory response by targeting GluD1 thereby alleviating resiniferatoxin-induced postherpetic neuralgia in mice. Journal of neuropathology and experimental neurology 0 41144370
2026 Integrated network pharmacology and multi-omics reveals GLUD1-mediated α-KG/Glu conversion in regulating amino acid metabolism: a mechanism of Dangua Fang against type 2 diabetes mellitus. Journal of ethnopharmacology 0 41529805
2026 METTL3-mediated GLUD1 m6A Modification Promotes Hydrogen Peroxide-induced Mitochondrial Dysfunction in Human Nucleus Pulposus Cells Via the Glutamate/α-KG Metabolic Axis. Journal of musculoskeletal & neuronal interactions 0 41764762
2026 GLUD1 supports ovarian cancer progression by counteracting anoikis via ARAF/MEK/ERK signaling. NPJ precision oncology 0 41786885
2026 AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression. Cell death & disease 0 41876450
2026 Echinacoside modulates PARP14-GLUD1 axis to mediate energy metabolism reprogramming and mitochondrial function in diminished ovarian reserve. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41895093
2026 Chronic Stress Promotes Oral Squamous Cell Carcinoma Progression via GLUD1-Mediated Metabolic Reprogramming. Carcinogenesis 0 41973845
2026 Molecular basis for ligand-gating of the human GluD1 receptor. bioRxiv : the preprint server for biology 0 41993446
2026 Hepatic IFRD1 suppresses metabolic dysfunction-associated fatty liver disease via GLUD1/α-KG axis. Science bulletin 0 41997855
2025 Hyperinsulinism-hyperammonemia syndrome associated with GLUD1 gene mutation: a case series. Journal of medical case reports 0 40652260
2025 GluD1 at the synaptic crossroads: from domain structure to circuit dysfunction. Acta pharmacologica Sinica 0 41345253
2023 Structural insights into the ligand binding domain of GluD1 and GluD2 receptors. The FEBS journal 0 37345272
2010 [Mutation analysis of the GLUD1 gene in patients with glutamate dehydrogenase congenital hyperinsulinism]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 20931523
1999 Identification of a novel single base-pair polymorphism in the glutamate dehydrogenase (GLUD1) gene. Journal of human genetics 0 10429370