Affinage

GLUD2

Glutamate dehydrogenase 2, mitochondrial · UniProt P49448

Length
558 aa
Mass
61.4 kDa
Annotated
2026-06-10
52 papers in source corpus 19 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GLUD2 encodes hGDH2, a human-specific mitochondrial glutamate dehydrogenase isoenzyme whose defining feature is a regulatory rewiring that dissociates catalysis from the GTP inhibition that controls the housekeeping isoenzyme hGDH1, leaving hGDH2 governed almost entirely by activation through ADP and L-leucine (PMID:11032875, PMID:17253646, PMID:17924438). Two evolutionary amino acid substitutions account for this adaptation: Gly456Ala confers GTP resistance, while Arg443Ser collapses basal activity to a few percent of maximal capacity and renders the enzyme dependent on ADP for function (PMID:12742085, PMID:22658952); the same regulatory domain — comprising the antenna and pivot helix — tunes basal activity, allosteric responsiveness, and thermostability, and Arg443Ser additionally confers heightened sensitivity to inhibition by estrogens, neuroleptics, spermidine, and EGCG (PMID:19393024, PMID:21420458). This regulatory design allows hGDH2 to oxidize glutamate under high-energy conditions that silence hGDH1, feeding carbon into the TCA cycle (PMID:11032875, PMID:27118840). The protein is imported into mitochondria via an N-terminal amphipathic leader helix that is necessary and sufficient for import (PMID:19448744, PMID:22709669), and is expressed in brain astrocytes and cortical neurons, testicular Sertoli cells, kidney proximal tubule, and steroidogenic tissues, with a cellular distribution distinct from hGDH1 (PMID:20194501, PMID:22709674, PMID:26399640). Functionally, hGDH2 supports synaptic plasticity through enhanced hippocampal LTP and dendritic spine density via lactate-dependent glia-neuron interaction (PMID:38791334), sustains ADP-driven basal insulin secretion during fasting (PMID:31400387), and rescues glutamine/glucose carbon flux to lipids and tumor growth in IDH1-mutant glioma (PMID:25225364). A gain-of-function Ser445Ala variant elevates basal activity and, when overexpressed in nigral dopaminergic neurons, exacerbates neurodegeneration by impairing succinate dehydrogenase activity and TCA cycle flux (PMID:19826450, PMID:33093440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Established that the GLUD2 product hGDH2 is a regulatorily distinct isoenzyme rather than a redundant copy, by showing it is completely insensitive to GTP and hyperresponsive to L-leucine.

    Evidence Enzyme kinetics on purified recombinant hGDH2 vs hGDH1 expressed in Sf9 cells, testing GTP, ADP, and L-leucine

    PMID:11032875

    Open questions at the time
    • Did not identify which residues confer the altered regulation
    • Tested in vitro only, not in cellular context
  2. 2003 High

    Pinpointed the molecular basis of hGDH2's adaptation by showing two substitutions (Gly456Ala for GTP resistance, Arg443Ser for ADP-dependence) recapitulate the key regulatory differences.

    Evidence Site-directed mutagenesis of GLUD1 to GLUD2-corresponding positions with kinetic characterization of recombinant proteins

    PMID:12742085

    Open questions at the time
    • Did not test whether the two changes alone fully reconstitute hGDH2 behavior
    • No structural model of the altered regulatory site
  3. 2007 High

    Refined the regulatory model by showing the two key substitutions are necessary but insufficient, implicating additional cooperating residues and pH tuning to the synaptic astrocyte environment.

    Evidence Recombinant reconstitution, double-mutant analysis, and pH-activity profiling (two corroborating publications)

    PMID:17253646 PMID:17924438

    Open questions at the time
    • Identity of the additional contributing residues not defined
    • Physiological pH environment inferred, not measured in situ
  4. 2009 High

    Defined the regulatory domain architecture (antenna vs pivot helix) and assigned distinct roles to its residues in setting basal activity, allosteric responsiveness, and thermostability.

    Evidence Panel of site-directed mutations in the hGDH2 regulatory domain with kinetic and thermostability assays

    PMID:19393024

    Open questions at the time
    • Structural mechanism linking heat lability to allosteric impairment not resolved
    • Single lab
  5. 2009 High

    Connected GLUD2 regulatory variation to disease by characterizing a gain-of-function Ser445Ala variant with elevated GTP-resistant basal activity and estrogen sensitivity.

    Evidence Recombinant kinetic and allosteric characterization of the Ala445-hGDH2 variant, with genetic association across PD cohorts

    PMID:19826450

    Open questions at the time
    • Causal mechanism in neurons not addressed at this stage
    • Effect size of genetic association limited
  6. 2009 High

    Determined how hGDH2 reaches its functional compartment, establishing mitochondrial localization with a minor ER pool and a signal-sequence-dependent import requirement.

    Evidence EGFP fusion confocal imaging with organelle markers, deletion mutagenesis, and Western fractionation across five cell lines

    PMID:19448744

    Open questions at the time
    • Functional significance of the ER-associated unprocessed pool unknown
    • Overexpression of fusion construct may not reflect endogenous targeting
  7. 2010 High

    Confirmed endogenous mitochondrial localization of hGDH2 in specific human cell types using an isoform-specific antibody, validating the recombinant findings in native tissue.

    Evidence Isoform-specific anti-hGDH2 antibody ICC/IF/Western and fractionation in human testis and cortex

    PMID:20194501

    Open questions at the time
    • Faint neuronal signal left neuronal expression unresolved
    • Did not address function in these cell types
  8. 2012 High

    Quantified hGDH2's low basal activity (3–8% of maximal) and attributed it primarily to Arg443Ser, while mapping its differential pharmacological inhibitor sensitivity.

    Evidence Recombinant kinetics in Sf21 cells with allosteric activation/inhibition assays

    PMID:22658952

    Open questions at the time
    • Physiological relevance of inhibitor sensitivities in vivo not established
  9. 2012 High

    Localized the mitochondrial import signal to the first N-terminal amphipathic alpha-helix, shown necessary and sufficient for targeting.

    Evidence Systematic GLUD2-EGFP leader deletion constructs with confocal imaging in three cell lines

    PMID:22709669

    Open questions at the time
    • Identity of the import receptor/machinery not defined
    • Based on fusion constructs
  10. 2012 Medium

    Expanded the tissue map showing hGDH2 occupies a distinct expression niche from hGDH1, including Sertoli cells and kidney proximal tubule.

    Evidence Isoform-specific antibody Western, IHC, and fractionation across human tissues

    PMID:22709674

    Open questions at the time
    • Single lab
    • Functional consequence of tissue-specific distribution not tested
  11. 2014 High

    Demonstrated a metabolic role for GLUD2 in cancer by showing it rescues glutamine/glucose carbon flux to lipids and tumor growth in IDH1-mutant glioma.

    Evidence Retroviral GLUD2 introduction with 13C flux tracing, shRNA knockdown, and orthotopic tumor assays

    PMID:25225364

    Open questions at the time
    • Used murine glioma model and combined GLUD1/2 knockdown
    • GLUD2-specific contribution vs GLUD1 not fully separated in vivo
  12. 2015 Medium

    Linked hGDH2 to steroidogenic and neuronal contexts, finding expression matched to the cholesterol side-chain cleavage system and in presynaptic neuronal mitochondria.

    Evidence Isoform-specific antibody IHC/IF with steroid hormone interaction assays and neuronal double-labeling in human tissue

    PMID:26241911 PMID:26399640

    Open questions at the time
    • Functional role in steroidogenic and presynaptic compartments not directly tested
    • Single lab
  13. 2016 Medium

    Provided in vivo evidence that GLUD2 reshapes TCA cycle carbon flux during brain development without altering glutamate pools.

    Evidence GLUD2 BAC transgenic mice with transcriptome and metabolome profiling during postnatal development

    PMID:27118840

    Open questions at the time
    • Lipid biosynthesis link inferred rather than measured
    • Mechanism connecting flux changes to developmental genes unresolved
  14. 2019 Medium

    Showed a physiological metabolic output of hGDH2 in vivo, sustaining elevated fasting insulin via ADP-driven glutamate flux.

    Evidence GLUD2 transgenic mice with fasting glucose/insulin measurement and leucine/glucose challenge

    PMID:31400387

    Open questions at the time
    • Direct demonstration of beta-cell glutamate flux not performed
    • Single lab
  15. 2020 High

    Established the disease mechanism of the Ser445Ala gain-of-function variant, linking it to dopaminergic neurodegeneration through succinate dehydrogenase inhibition and TCA cycle impairment.

    Evidence AAV delivery of GLUD2 Ser445Ala into substantia nigra of MPTP mice with behavioral, metabolomic, enzymatic, and molecular readouts

    PMID:33093440

    Open questions at the time
    • Causal chain from SDH inhibition to BDNF/Nrf2 downregulation not fully dissected
    • Overexpression model
  16. 2024 Medium

    Connected hGDH2 to synaptic plasticity by showing it enhances hippocampal LTP and dendritic spine density through lactate-dependent glia-neuron interaction.

    Evidence GLUD2 transgenic mouse LTP field recordings, CA1 patch-clamp, D-lactate block, spine counting, and cognitive testing

    PMID:38791334

    Open questions at the time
    • Mechanism of lactate dependence needs further validation
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous physiological substrate flux and in vivo regulatory state of hGDH2 across its tissue niches, and how its low basal activity is dynamically engaged, remain incompletely defined.
  • No structural model of the rewired regulatory site reported in the corpus
  • Direct in situ measurement of ADP/leucine-driven hGDH2 activation lacking
  • Functional role in steroidogenic and renal tissues uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 4 GO:0098772 molecular function regulator activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005739 mitochondrion 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-112316 Neuronal System 1

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Recombinant GLUD2-encoded hGDH2 is completely insensitive to GTP inhibition (IC50 >5,000 µM) unlike GLUD1-encoded hGDH1 (IC50 = 0.20 µM), and shows ~1,600% activation by 1.0 mM L-leucine versus ~75% for hGDH1. ADP synergizes with L-leucine to permit activation at physiologically relevant concentrations. These distinct allosteric mechanisms were established using purified recombinant enzymes expressed in Sf9 cells. Recombinant protein expression in Sf9 cells; enzyme kinetics; allosteric regulation assays with GTP, ADP, L-leucine Journal of neurochemistry High 11032875
2003 Site-directed mutagenesis of GLUD1 at positions corresponding to GLUD2 differences showed that Gly456Ala substitution confers GTP resistance (IC50 raised from 0.19 to 2.8 µM) and Arg443Ser substitution virtually abolishes basal activity while rendering the enzyme dependent on ADP for function. These two substitutions are the main evolutionary changes responsible for hGDH2's adaptation to nerve tissue. Site-directed mutagenesis of GLUD1; enzyme kinetic assays; recombinant protein expression Neurochemistry international High 12742085
2007 Purified recombinant wild-type hGDH2 is dissociated from GTP control, regulated almost entirely by ADP and/or L-leucine, and has activity fine-tuned to the relatively low cellular pH of synaptic astrocytes. A double hGDH1 mutant carrying both Arg443Ser and Gly456Ala did not fully recapitulate all properties of hGDH2, indicating that additional amino acid changes act in concert with these two substitutions. Recombinant protein expression and purification; enzyme kinetics; site-directed mutagenesis; pH-activity profiling Journal of neuroscience research High 17253646 17924438
2009 GLUD2/EGFP fusion constructs transfected into COS7, HeLa, CHO, HEK293, and SHSY-5Y cells co-localize predominantly with mitochondrial marker DsRed2-Mito and to a lesser extent with ER marker DsRed2-ER. Deletion of the signal sequence prevents mitochondrial entry. Western blot identifies a ~90 kDa mitochondrial band and a ~95 kDa ER-associated band representing full-length unprocessed hGDH2. Confocal microscopy of EGFP fusions; co-transfection with organelle markers; Western blot fractionation; deletion mutagenesis Biochemistry and cell biology High 19448744
2009 A rare gain-of-function GLUD2 variant (T1492G; Ser445Ala) shows enhanced basal catalytic activity that is resistant to GTP inhibition but markedly sensitive to modulation by estrogens. This was established by biochemical analysis of the recombinant Ala445-hGDH2 variant. Recombinant protein expression; enzyme kinetics; allosteric modulation assays with GTP and estrogens European journal of human genetics High 19826450
2009 Site-directed mutations in the regulatory domain (antenna and pivot helix) of hGDH2 reveal distinct roles: antenna mutations (Gln441Arg, Ser445Leu) increase basal activity without altering allosteric properties; pivot helix mutations (Lys450Glu, His454Tyr) drastically reduce basal activity and impair regulation; Ser448Pro reduces basal activity but leaves allosteric regulation intact. Pivot helix mutants are extremely heat labile, while antenna mutants are relatively thermostable. Site-directed mutagenesis of hGDH2; enzyme kinetics; thermostability assays; recombinant protein expression Journal of neurochemistry High 19393024
2010 Endogenous hGDH2 protein localizes to mitochondria in human testicular Sertoli cells and cerebral cortical astrocytes, as shown using a specific anti-hGDH2 antibody developed against the Ser443-containing epitope (residues 436–447). Western blot confirmed mitochondrial fractionation. Neurons showed only faint hGDH2 immunoreactivity in this study. Immunocytochemistry; immunofluorescence; Western blot with isoform-specific antibody; subcellular fractionation The Journal of biological chemistry High 20194501
2011 hGDH2 has dissociated its catalytic function from GTP control and can metabolize glutamate even when Krebs cycle-generated GTP levels are sufficient to inactivate hGDH1. Estrogens and neuroleptic drugs (haloperidol, perphenazine) inhibit hGDH2 more potently than hGDH1, and the evolutionary Arg443Ser substitution is largely responsible for this differential sensitivity. Recombinant enzyme assays; pharmacological inhibition studies; site-directed mutagenesis Neurochemistry international High 21420458
2012 Purified recombinant hGDH2 maintains a baseline activity of 3–8% of maximal capacity (versus 35–40% for hGDH1), conferred primarily by the Arg443Ser evolutionary change. This low basal activity is fully responsive to activation by rising ADP and/or L-leucine. The Arg443Ser change also makes hGDH2 markedly sensitive to inhibition by estrogens, spermidine, and EGCG at lower concentrations than hGDH1. Recombinant protein expression in Sf21 cells; enzyme kinetics; allosteric activation and inhibition assays Neurochemistry international High 22658952
2012 The first N-terminal amphipathic alpha-helix of the hGDH2 leader sequence is necessary and sufficient for mitochondrial import. Deletion of the entire leader sequence or of only this first alpha-helix prevented mitochondrial localization of GLUD2-EGFP constructs in HEK293, COS7, and SHSY-5Y cells, retaining the protein in the cytoplasm. Truncated leaders retaining only the second and/or third helices failed to restore import. Secondary structure prediction; GLUD2-EGFP deletion constructs; confocal microscopy with mitochondrial co-marker in three mammalian cell lines Neurochemistry international High 22709669
2012 hGDH2 (and hGDH1) is expressed in testis mitochondrial fraction and in brain astrocytes as shown by Western blot using isoform-specific antibody. hGDH2 is also expressed in kidney proximal tubule epithelial cells. The two isoenzymes display distinct cellular distributions: Sertoli cells are strongly positive for hGDH2 but negative for hGDH1, while liver hepatocytes express very high hGDH1 but virtually no hGDH2. Isoform-specific antibodies; Western blot; immunohistochemistry; subcellular fractionation Neurochemistry international Medium 22709674
2014 Introduction of GLUD2 into murine glioma progenitor cells reverses the growth-inhibitory and metabolic flux defects caused by IDH1(R132H) mutation: GLUD2 expression rescues flux from glutamine and glucose to lipids and restores tumor growth. Orthotopic growth of IDH1-mutant glioma is inhibited by GLUD1/2 knockdown. Glutamate, a GLUD2 substrate, supports glioma progenitor cell growth irrespective of IDH1 status. Retroviral introduction of GLUD2 into murine glioma cells; metabolic flux analysis (13C tracing); orthotopic tumor implantation; shRNA knockdown; cell growth assays Proceedings of the National Academy of Sciences of the United States of America High 25225364
2015 hGDH2 is expressed in steroid-producing cells of adrenal cortex, testis, ovaries, and placenta. Steroid hormones interact differentially with hGDH1 and hGDH2. The distinct expression of hGDH2 (but not hGDH1) in Sertoli cells and matching of hGDH2 expression with the cholesterol side chain cleavage system in adrenals was established using isoform-specific antibodies. Immunohistochemistry with isoform-specific antibodies; functional steroid hormone interaction assays Molecular and cellular endocrinology Medium 26241911
2015 hGDH2 immunoreactivity is detected in the cytoplasm of large cortical neurons within structures resembling mitochondria, distributed either in the perikaryon or in the cell periphery near synaptic terminals, in addition to astrocytes. Double immunofluorescence suggests that peripheral neuronal hGDH2 labels presynaptic mitochondria. This contrasts with hGDH1, which is restricted to glial cells. Immunohistochemistry; immunofluorescence with confocal microscopy; double labeling with glial and neuronal markers; isoform-specific antibodies on human cortical tissue Molecular neurobiology Medium 26399640
2016 Transgenic mice carrying the human GLUD2 gene show metabolic effects centered on the tricarboxylic acid cycle during postnatal brain development, affecting genes involved in neuronal development. GLUD2 introduction did not affect glutamate levels but altered TCA cycle metabolites, suggesting GLUD2 affects carbon flux, possibly supporting lipid biosynthesis during early brain development. Transgenic mice (BAC insertion of human GLUD2); transcriptome analysis; metabolome analysis during postnatal brain development Proceedings of the National Academy of Sciences of the United States of America Medium 27118840
2019 Expression of hGDH2 in pancreatic β-cells of GLUD2 transgenic mice maintains 2.6-fold higher fasting serum insulin levels and lower fasting blood glucose compared to wild-type. L-leucine had little effect on already-high insulin in Tg mice, suggesting that under high ADP levels prevailing during fasting, hGDH2-mediated glutamate flux is near maximal. GLUD2 does not significantly affect glucose-stimulated insulin secretion. GLUD2 transgenic mice; fasting blood glucose measurement; serum insulin ELISA; L-leucine and glucose challenge tests; isoform-specific antibody confirmation of β-cell expression Metabolism: clinical and experimental Medium 31400387
2020 AAV-expressed GLUD2 Ser445Ala gain-of-function mutant in the substantia nigra of MPTP-PD model mice exacerbates dopaminergic neuron death, movement deficits, reduces glutamate transporter expression/function, and damages mitochondrial function by decreasing succinate dehydrogenase activity to impede the TCA cycle. Downregulation of BDNF/Nrf2 signaling was also identified as a downstream consequence. AAV-mediated in vivo gene delivery; MPTP mouse model; behavioral testing; metabolomics (GC-Q-TOF/MS); succinate dehydrogenase activity assay; Western blot; glutamate transporter functional assay Cell death & disease High 33093440
2024 In GLUD2 transgenic mice, theta-burst-evoked long-term potentiation (LTP) is markedly enhanced at hippocampal CA3-CA1 synapses, with patch-clamp recordings revealing increased spontaneous NMDA receptor currents in CA1 pyramidal neurons. D-lactate blocked LTP enhancement, implicating L-lactate-dependent glia-neuron interaction as the mechanism. Transgenic mice also exhibit increased dendritic spine density and improved complex cognitive functions. GLUD2 transgenic mice; field recordings of theta-burst LTP; whole-cell patch-clamp of CA1 neurons; D-lactate pharmacological block; dendritic spine counting; behavioral cognitive testing International journal of molecular sciences Medium 38791334

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Hominoid-specific enzyme GLUD2 promotes growth of IDH1R132H glioma. Proceedings of the National Academy of Sciences of the United States of America 90 25225364
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
2013 Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO reports 67 24357660
2010 Human GLUD2 glutamate dehydrogenase is expressed in neural and testicular supporting cells. The Journal of biological chemistry 58 20194501
2009 The N-terminal domain of GluD2 (GluRdelta2) recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 19420242
2003 Study of structure-function relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissue-specific (GLUD2) isoenzyme. Neurochemistry international 56 12742085
2012 Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. Neuron 48 23141067
2011 The human GLUD2 glutamate dehydrogenase and its regulation in health and disease. Neurochemistry international 48 21420458
2009 Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and endoplasmic reticulum. Biochemistry and cell biology = Biochimie et biologie cellulaire 47 19448744
2009 Gain-of-function variant in GLUD2 glutamate dehydrogenase modifies Parkinson's disease onset. European journal of human genetics : EJHG 44 19826450
2020 GluD2- and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells. Neuron 38 33352118
2019 Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. The Journal of comparative neurology 38 31625608
2013 The discovery of human of GLUD2 glutamate dehydrogenase and its implications for cell function in health and disease. Neurochemical research 37 24352816
2012 Cerebellar LTD vs. motor learning-lessons learned from studying GluD2. Neural networks : the official journal of the International Neural Network Society 37 22840919
2012 Expression of human GLUD2 glutamate dehydrogenase in human tissues: functional implications. Neurochemistry international 33 22709674
2016 Mice carrying a human GLUD2 gene recapitulate aspects of human transcriptome and metabolome development. Proceedings of the National Academy of Sciences of the United States of America 31 27118840
2009 The human GLUD2 glutamate dehydrogenase: localization and functional aspects. Neurochemistry international 30 19428807
2020 The architecture of GluD2 ionotropic delta glutamate receptor elucidated by cryo-EM. Journal of structural biology 28 32512155
2016 GluD2 Endows Parallel Fiber-Purkinje Cell Synapses with a High Regenerative Capacity. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 27122040
2016 mGlu1 receptor canonical signaling pathway contributes to the opening of the orphan GluD2 receptor. Neuropharmacology 27 27276689
2012 The complex regulation of human glud1 and glud2 glutamate dehydrogenases and its implications in nerve tissue biology. Neurochemistry international 27 22658952
2018 Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression. EBioMedicine 25 30314897
2015 Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors. Molecular pharmacology 25 26661043
2017 Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features. BMC medical genetics 24 29207948
2007 Properties and molecular evolution of human GLUD2 (neural and testicular tissue-specific) glutamate dehydrogenase. Journal of neuroscience research 22 17253646
2020 Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology. eLife 21 33112237
2015 Expression of human GLUD1 and GLUD2 glutamate dehydrogenases in steroid producing tissues. Molecular and cellular endocrinology 21 26241911
2007 Properties and molecular evolution of human GLUD2 (neural and testicular tissue-specific) glutamate dehydrogenase. Journal of neuroscience research 21 17924438
2020 Functional validation of a human GLUD2 variant in a murine model of Parkinson's disease. Cell death & disease 19 33093440
2016 Widening Spectrum of Cellular and Subcellular Expression of Human GLUD1 and GLUD2 Glutamate Dehydrogenases Suggests Novel Functions. Neurochemical research 19 27422263
2013 Disruption of cerebellar microzonal organization in GluD2 (GluRδ2) knockout mouse. Frontiers in neural circuits 19 23970854
2017 Cbln1 and Cbln4 Are Structurally Similar but Differ in GluD2 Binding Interactions. Cell reports 18 28877468
2021 Role of Glutamine-Glutamate/GABA cycle and potential target GLUD2 in alleviation of rheumatoid arthritis by Tripterygium hypoglaucum (levl.) Hutch based on metabolomics and molecular pharmacology. Journal of ethnopharmacology 17 34454056
1998 Evaluation of two X chromosomal candidate genes for Rett syndrome: glutamate dehydrogenase-2 (GLUD2) and rab GDP-dissociation inhibitor (GDI1). American journal of medical genetics 17 9674910
2020 D-Serine Potently Drives Ligand-Binding Domain Closure in the Ionotropic Glutamate Receptor GluD2. Structure (London, England : 1993) 16 32735769
2017 The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region. Scientific reports 16 28387240
2015 Evolution of GLUD2 Glutamate Dehydrogenase Allows Expression in Human Cortical Neurons. Molecular neurobiology 16 26399640
2022 Differences between the GluD1 and GluD2 receptors revealed by GluD1 X-ray crystallography, binding studies and molecular dynamics. The FEBS journal 14 36128700
2012 Alpha helical structures in the leader sequence of human GLUD2 glutamate dehydrogenase responsible for mitochondrial import. Neurochemistry international 12 22709669
2013 Contribution of postsynaptic GluD2 to presynaptic R-type Ca(2+) channel function, glutamate release and long-term potentiation at parallel fiber to Purkinje cell synapses. Cerebellum (London, England) 11 23564161
2009 Mutations in human GLUD2 glutamate dehydrogenase affecting basal activity and regulation. Journal of neurochemistry 11 19393024
2018 Transgenic Mice Carrying GLUD2 as a Tool for Studying the Expressional and the Functional Adaptation of this Positive Selected Gene in Human Brain Evolution. Neurochemical research 9 29777493
2010 Flap loop of GluD2 binds to Cbln1 and induces presynaptic differentiation. Biochemical and biophysical research communications 7 20599760
2024 Evolution of Glutamate Metabolism via GLUD2 Enhances Lactate-Dependent Synaptic Plasticity and Complex Cognition. International journal of molecular sciences 6 38791334
2020 Absence of GluD2 Antibodies in Patients With Opsoclonus-Myoclonus Syndrome. Neurology 6 33443132
2012 The ins and outs of GluD2--why and how Purkinje cells use the special glutamate receptor. Cerebellum (London, England) 6 22113500
2016 Developmental Hypothyroxinemia and Hypothyroidism Reduce Parallel Fiber-Purkinje Cell Synapses in Rat Offspring by Downregulation of Neurexin1/Cbln1/GluD2 Tripartite Complex. Biological trace element research 4 27033232
2019 Transgenic expression of the positive selected human GLUD2 gene improves in vivo glucose homeostasis by regulating basic insulin secretion. Metabolism: clinical and experimental 3 31400387
2004 [Fine mapping of Smith-Fineman-Myers syndrome and exclusion of GPC3, GPCR2 MST4 and GLUD2 as candidate genes]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2 15192816
2016 Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice. PloS one 1 27820843
1991 Confirmation, via in situ hybridization, of the occurrence of Robertsonian translocations during lemur evolution by localization of GLUDP1 DNA sequences on lemur chromosomes. Cytogenetics and cell genetics 1 1855394
2023 Structural insights into the ligand binding domain of GluD1 and GluD2 receptors. The FEBS journal 0 37345272

Missed literature

Know a paper Affinage missed for GLUD2? Flag it for the maintainers and the community.

No submissions yet.