Affinage

GRIA4

Glutamate receptor 4 · UniProt P48058

Length
902 aa
Mass
100.9 kDa
Annotated
2026-04-28
44 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIA4 encodes GluA4, an AMPA-type ionotropic glutamate receptor subunit that serves as the principal fast-kinetics AMPAR at multiple central synapses—including reticular thalamic neurons, cerebellar granule cells, auditory relay nuclei, and immature hippocampal pyramidal cells—where it is essential for high-fidelity synaptic transmission, circuit synchrony, and developmental plasticity (PMID:18316356, PMID:34219651, PMID:26390982, PMID:24599589). Structurally, GluA4 assembles into a Y-shaped tetramer with domain-swapped NTD/LBD dimer pairs; the N-terminal domain mediates dimerization while the S1-S2 ligand-binding domain binds glutamate with high affinity, stabilized by a buried C260–C315 disulfide bond, and ion channel opening proceeds through asymmetric hinging of all four channel helices with LBD conformational plasticity tuning subconductance states (PMID:41656278, PMID:10506139, PMID:9737972, PMID:8663017). TARP auxiliary subunits (stargazin/γ-4) engage a regulatory site within the ligand-binding domain to slow both opening and closing rates and modulate desensitization kinetics; surface trafficking requires a C-terminal 14-residue segment that binds protein 4.1 family members, while a conserved C-terminal proline precludes canonical PDZ interactions with SAP97 (PMID:40954371, PMID:31267004, PMID:12574408, PMID:20090852). In neonatal hippocampus, PKA-driven synaptic insertion of GluA4 defines the mechanism for early-life LTP and homeostatic plasticity, and Gria4 loss causes absence seizures linked to altered thalamocortical synchrony (PMID:24599589, PMID:26961102, PMID:18316356).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Establishing that the GluA4 ligand-binding domain can be reconstituted as a soluble S1-S2 fusion with native-like AMPA pharmacology showed that ligand recognition is an intrinsic property of this domain, independent of the full receptor and N-glycosylation.

    Evidence Bacterial expression of S1-S2 fusion protein with [3H]AMPA radioligand binding and deletion mutagenesis

    PMID:8663017

    Open questions at the time
    • No channel function measured from isolated domain
    • Agonist vs. antagonist binding determinants not yet mapped
  2. 1998 High

    Identification of a buried C260–C315 disulfide bond in the ligand-binding domain resolved why GluA4 is insensitive to redox modulation and showed the disulfide constrains domain conformation to maintain proper oligomerization and binding activity.

    Evidence Biochemical disulfide detection, site-directed mutagenesis, ligand binding assays

    PMID:9737972

    Open questions at the time
    • No structural data at atomic resolution
    • Whether the disulfide functions identically in heteromeric assemblies was untested
  3. 1999 High

    Demonstrating that the N-terminal (X) domain mediates dimerization while the S1-S2 domain is monomeric established the modular architecture of GluA4 ectodomain assembly, separating oligomerization from ligand binding.

    Evidence Hydrodynamic analysis of recombinant ectodomain fragments; radiolabeled ligand binding

    PMID:10506139

    Open questions at the time
    • Tetrameric assembly mechanism not yet resolved
    • No structural visualization of the full ectodomain
  4. 2002 High

    Systematic mutagenesis of helix F (lobe 2) and interdomain ionic residues delineated which side chains in the LBD selectively engage agonists versus antagonists, providing a mechanistic basis for activation-specific conformational changes.

    Evidence Site-directed mutagenesis with [3H]AMPA and [3H]Ro 48-8587 radioligand binding assays and computational docking

    PMID:12167621 PMID:12473122

    Open questions at the time
    • No electrophysiological correlate of mutant function
    • No crystal structure of LBD with bound ligand at this time
  5. 2003 High

    Identifying a 14-residue C-terminal segment that binds protein 4.1 family members and is required for surface expression revealed the primary trafficking determinant for GluA4-containing AMPARs, distinct from PDZ-based mechanisms used by other subunits.

    Evidence C-terminal deletion analysis, GST pull-down, co-IP from HEK293 cells and rat brain, surface ELISA

    PMID:12574408

    Open questions at the time
    • Which 4.1 family member is most relevant in vivo unknown
    • Whether this segment also controls synaptic versus extrasynaptic localization was untested
  6. 2008 High

    The finding that Gria4-knockout mice exhibit absence seizures with enhanced reticular thalamic neuron excitation established GluA4 as essential for thalamocortical circuit synchrony and linked it to epilepsy pathogenesis.

    Evidence Gria4-KO mice with EEG, electrophysiology, and genetic epistasis with Gria3

    PMID:18316356

    Open questions at the time
    • Cell-type-specific rescue not performed
    • Human genetic confirmation not yet available at the time
  7. 2010 High

    Demonstrating that a conserved C-terminal proline blocks canonical PDZ binding to SAP97, with mass spectrometry confirming the proline is not cleaved in vivo, resolved conflicting reports of GluA4–SAP97 association and showed this interaction is necessarily indirect.

    Evidence Co-IP, mass spectrometry, proline-deletion mutant

    PMID:20090852

    Open questions at the time
    • The bridging molecule mediating indirect SAP97 association not identified
  8. 2011 High

    Optogenetic circuit dissection in Gria4-KO mice revealed that weakened cortico-nRT excitation enables a bypass cortico-TC-nRT-TC pathway to initiate oscillations, explaining how selective loss of GluA4 at one synapse type reorganizes thalamocortical dynamics.

    Evidence In vivo optogenetics, whole-cell electrophysiology, EEG in Gria4-KO mice

    PMID:21857658

    Open questions at the time
    • Whether compensatory changes in other receptor types contribute was not excluded
  9. 2014 High

    Showing that GluA4 is both necessary and sufficient for neonatal PKA-dependent LTP in CA1—and that lentiviral re-expression at any age restores it—established GluA4 as the molecular determinant of the developmental switch in LTP kinase dependency from PKA to CaMKII.

    Evidence GluA4-KO mice, lentiviral rescue, electrophysiology, PKA pharmacology

    PMID:24599589 PMID:27157711

    Open questions at the time
    • Phosphorylation site(s) on GluA4 mediating PKA-driven insertion not identified
    • Whether GluA4 is sufficient in non-hippocampal circuits unknown
  10. 2016 High

    GluA4-KO mice lacking both homeostatic upregulation and Hebbian weakening at neonatal hippocampal synapses demonstrated that GluA4 is the shared effector for both forms of early-life plasticity, not just Hebbian LTP.

    Evidence GluA4-KO mice with TTX activity-blockade paradigm, whole-cell electrophysiology

    PMID:26961102

    Open questions at the time
    • Downstream signaling cascade linking activity blockade to GluA4 insertion not mapped
  11. 2019 High

    Kinetic measurements showing TARPs γ-2 and γ-4 slow GluA4 opening and closing rates 3–4-fold without changing open probability quantified how auxiliary subunits tune GluA4 channel kinetics, with γ-4 preferentially slowing desensitization.

    Evidence Laser-pulse photolysis rapid-perfusion electrophysiology measuring kop and kcl

    PMID:31267004

    Open questions at the time
    • Structural basis of differential TARP effects unknown at the time
  12. 2021 High

    ~80% loss of mossy fiber-to-granule cell transmission in GluA4-KO mice with failure of eyeblink conditioning established GluA4 as the essential AMPAR subunit for cerebellar expansion coding and associative motor learning.

    Evidence GluA4-KO mice, electrophysiology at mossy fiber–granule cell synapses, computational modeling, eyeblink conditioning

    PMID:34219651

    Open questions at the time
    • Whether GluA4 loss affects Purkinje cell-dependent plasticity not tested
    • Contribution of heteromeric GluA4 assemblies versus homomers not resolved
  13. 2025 High

    Cryo-EM structures of GluA4 alone and in complex with TARP-γ2 across resting, active, and desensitized states revealed that ion channel opening occurs via asymmetric hinging of all four channel helices, that LBD conformational plasticity tunes subconductance states, and that TARP-γ2 engages a specific regulatory site in the LBD.

    Evidence Cryo-EM structures with functional validation by single-channel bilayer recordings

    PMID:40954371 PMID:41656278

    Open questions at the time
    • Structures of GluA4 heteromeric assemblies (e.g. GluA2/4) not yet solved
    • How TARP regulatory site engagement translates to kinetic rate changes at atomic level not fully modeled

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the specific PKA phosphorylation site(s) on GluA4 that drive synaptic insertion, the identity of the bridging partner enabling indirect GluA4–SAP97 association in vivo, and whether GluA4 heteromeric complexes adopt distinct structural conformations compared to homomers.
  • PKA phosphorylation site on GluA4 not mapped
  • Bridging molecule for SAP97 association unknown
  • No cryo-EM of GluA4-containing heteromeric AMPARs

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 3 R-HSA-382551 Transport of small molecules 3
Partners
EPB41 (PROTEIN 4.1)KSR1SAP97 (DLG1)TARP-Γ2 (STARGAZIN/CACNG2)TARP-Γ4 (CACNG4)
Complex memberships
AMPA receptor (GluA4 homomer)GluA4:TARP-γ2 complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 Cryo-EM structures of GluA4:TARP-γ2 complex trapped in active, resting, and desensitized states reveal that GluA4 AMPARs adopt a canonical Y-shaped conformation, open the ion channel via asymmetric hinging of all channel helices upon glutamate binding, and that TARP-γ2 has a regulatory site in the ligand-binding domain that modulates gating kinetics. Cryo-electron microscopy (cryo-EM) structures with functional validation Nature structural & molecular biology High 40954371
2026 Cryo-EM of GluA4 AMPARs shows a canonical Y-shaped architecture with domain-swapped NTD/LBD dimer pairs; all four LBDs bind glutamate yet ion channel opening occurs by asymmetric hinging of all four channel helices, and LBD conformational plasticity under saturating glutamate tunes subconductance states. Cryo-electron microscopy (cryo-EM) combined with single-channel bilayer recordings Nature communications High 41656278
2025 Cryo-EM of GluA4 alone reveals classical Y-shaped conformation; in resting conditions GluA4:TARP-γ2 adopts two conformations, one resembling the desensitized state of other GluA subunits, indicating subunit-specific structural dynamics. Cryo-electron microscopy (cryo-EM) bioRxiv (preprint)preprint Medium 40667226
2003 GluA4 (GluR-D) surface expression requires a 14-residue cytoplasmic C-terminal segment that mediates interaction with 4.1 family proteins; point mutations within this segment abolish both 4.1 binding and surface expression of homomeric GluA4 receptors. C-terminal deletion analysis, GST pull-down, co-immunoprecipitation from HEK293 cells and rat brain, surface ELISA The Journal of neuroscience High 12574408
1999 The N-terminal extracellular domain (X domain) of GluA4 mediates dimerization of the receptor ectodomain, whereas the S1S2 ligand-binding domain is monomeric; the X domain does not itself bind AMPA or glutamate. Hydrodynamic analysis (gel filtration, sedimentation) of recombinant soluble ectodomain fragments expressed in insect cells; radiolabeled ligand binding assays The Journal of biological chemistry High 10506139
1996 The ligand-binding domain of GluA4 (GluR-D) expressed as a soluble S1-S2 fusion protein in E. coli binds [3H]AMPA with high affinity (Kd ~60 nM) in a pharmacology typical of native AMPA receptors; N-glycosylation is not required for formation or maintenance of the ligand-binding site; deletion of the C-terminal one-third of S2 abolishes binding. Bacterial expression of S1-S2 fusion protein, [3H]AMPA radioligand binding assay, deletion mutagenesis The Journal of biological chemistry High 8663017
1998 A disulfide bond between conserved cysteines C260 and C315 exists in the ligand-binding domain of GluA4 (GluR-D); this disulfide is inaccessible to DTT in the intact receptor, explaining insensitivity to redox modulation. Single C260S and C315S mutants show 2-3-fold higher ligand affinity, and mutants lacking the disulfide show non-native oligomerization and dramatically reduced specific activity, indicating the disulfide stabilizes the ligand-binding domain. Biochemical disulfide detection, site-directed mutagenesis, ligand binding assays The Journal of biological chemistry High 9737972
2002 Site-directed mutagenesis of GluA4 ligand-binding domain identifies Leu-672 and Thr-677 in helix F (lobe 2) as critical for binding all agonists; mutations at Asp-673, Ser-674, Gly-675, Ser-676, and Lys-678 selectively affect specific agonists. In contrast, antagonist ([3H]Ro 48-8587, DNQX) binding is unaffected by any of these mutations, demonstrating selective engagement of helix F side chains in agonist binding and suggesting conformational changes in this region underlie receptor activation. Site-directed mutagenesis, [3H]AMPA and [3H]Ro 48-8587 radioligand competition binding assays, ligand docking The Journal of biological chemistry High 12167621
2002 Mutagenesis of GluA4 ligand-binding domain shows that R507 is essential for both agonist and antagonist binding (even conservative R507K abolishes binding), while E727 is essential for agonist binding but not for antagonist binding, revealing differential ionic interactions in agonist vs. antagonist recognition. Site-directed mutagenesis, [3H]AMPA and [3H]Ro 48-8587 radioligand binding assays, ligand docking European journal of biochemistry High 12473122
2010 Native GluA4's C-terminal PDZ motif is blocked by a conserved proline residue; deletion of this proline confers avid binding to SAP97. Mass spectrometric analysis of native brain GluA4 confirms the C-terminus is intact (proline not cleaved), so GluA4 does not engage canonical PDZ interactions and its association with SAP97 in vivo is indirect. Co-immunoprecipitation, mass spectrometry, generation of proline-deleted mutant and antibody against cleaved C-terminus PloS one High 20090852
2009 Ethanol concentration-dependently accelerates desensitization of GluA4 (GluR-D) homomeric receptors; co-expression of TARPs (stargazin/γ4) slows desensitization onset and increases steady-state current, and potentiates the ethanol-induced increase in desensitization rate. γ4 also slows recovery from desensitization but ethanol does not affect this step. Whole-cell electrophysiology in HEK293 cells expressing recombinant GluA4 ± TARPs, with ethanol application Alcohol Medium 19560629
2019 Both stargazin (γ-2) and γ-4 TARPs slow GluA4 channel opening (kop) and closing (kcl) rates ~3-4 fold without changing channel-opening probability; γ-4 more strongly slows desensitization while γ-2 produces a larger left-shift in glutamate dose-response relationship. Laser-pulse photolysis rapid-perfusion electrophysiology measuring channel-opening and closing rate constants Scientific reports High 31267004
2014 GluA4 expression in immature CA1 pyramidal neurons is sufficient to confer PKA-dependent LTP; PKA activation drives synaptic insertion of GluA4-containing AMPARs. In GluA4-deficient mice, neonatal PKA-dependent LTP is abolished. Lentiviral re-expression of GluA4 at any developmental stage restores PKA-dependent synaptic potentiation, establishing GluA4 as the molecular determinant of the developmental switch in LTP kinase dependency from PKA to CaMKII. GluA4-knockout mice, lentiviral GluA4 expression, whole-cell electrophysiology, pharmacological kinase manipulation PNAS High 24599589
2016 PKA activation drives insertion of GluA4 to synaptic sites with weak or silent AMPAR-mediated transmission; this requires the extreme C-terminal end of GluA4 which interacts with the membrane-proximal region of its own C-terminal domain to control trafficking. GluA4-deficient mice show significantly delayed strengthening of AMPAR-mediated transmission during postnatal development. Electrophysiology at CA1 synapses, GluA4-KO mice, C-terminal domain deletion/interaction analysis, PKA pharmacology Neuropharmacology High 27157711
2014 SAP97 forms the molecular backbone for sequential delivery of GluA4-containing AMPARs to synapses during classical conditioning; conditioning induces formation of a SAP97-KSR1/PKC-GluA4 complex that delivers GluA4 to synapses via a SAP97-PSD95 interaction. Co-immunoprecipitation, in vitro classical conditioning model, pharmacological kinase inhibition The Journal of biological chemistry Medium 24567325
2008 Gria4 knockout mice exhibit frequent spike-wave discharges (absence seizures). In Gria4 mutants, synaptic excitation of inhibitory reticular thalamic neurons is enhanced with increased duration of synaptic responses, consistent with loss of the kinetically faster AMPA receptor subunit encoded by Gria4. Gria3 loss in contrast lowers SWD, establishing genetic epistasis between Gria4 and Gria3 in thalamic circuit synchrony. Gria4 knockout mice, EEG recording, whole-cell electrophysiology, genetic epistasis (Gria3/Gria4 double mutant) Human molecular genetics High 18316356
2011 Gria4-deficient mice show selective reduction in synaptic strength at the cortico-reticular thalamic (nRT) projection but not at the cortico-TC pathway; this reveals that cortico-thalamo-cortical oscillations can be initiated via a cortico-TC-nRT-TC bypass pathway when direct cortico-nRT excitation is weakened. Gria4-KO mice, in vivo optogenetics, whole-cell electrophysiology, EEG Nature neuroscience High 21857658
2013 Repeated morphine treatment causes synaptic insertion of GluA4-containing (Ca2+-permeable) AMPARs in spinal cord dorsal horn laminae III-V; co-immunoprecipitation shows increased GluA4 homomers in the postsynaptic density; intracellular infusion of GluA4 antibody via patch pipette reverses increased EPSC rectification, directly implicating GluA4-containing AMPARs in morphine-induced mechanical hypersensitivity. Co-immunoprecipitation, western blotting of PSD fractions, whole-cell electrophysiology with Ca2+-permeable AMPAR blocker and intracellular antibody, immunohistochemistry Neuropsychopharmacology High 23403695
2021 GluA4-knockout mice show ~80% reduction in mossy fiber-to-granule cell synaptic transmission in the cerebellum, with decreased fidelity of granule cell spike output despite compensatory increases in NMDA receptor-mediated transmission and reduced tonic inhibition; GluA4-KO mice fail eyeblink conditioning but retain locomotor coordination, demonstrating an essential role for GluA4 in cerebellar expansion coding and associative memory formation. GluA4-KO mice, whole-cell electrophysiology at mossy fiber-granule cell synapses, computational network modeling, behavioral eyeblink conditioning eLife High 34219651
2015 Virus-mediated knockdown of GluA4 in POm relay neurons almost abolishes EPSC amplitude at the L5B-POm giant corticothalamic synapse, strongly delaying onset of postsynaptic action potential generation, establishing GluA4 as the primary AMPAR subunit responsible for the large-amplitude driver EPSCs at this synapse. Virus-mediated genetic knockdown, direct electrical stimulation of single corticothalamic terminals, whole-cell recording European journal of neuroscience High 26390982
2016 Acoustic trauma (AT) decreases GluA4 mRNA and increases GluA1 mRNA in the lateral superior olive, slowing AMPAR-EPSC decay kinetics; this change in subunit composition (replacement of fast GluA4 by slow GluA1) compensates for hearing loss by prolonging EPSCs to maintain binaural function, as confirmed by computational modeling. Voltage-clamp electrophysiology, RT-PCR, auditory brainstem responses, computational modeling The Journal of physiology Medium 27104476
2017 Quantitative freeze-fracture replica immunogold labeling shows GluA4 subunits are present at higher number and density at auditory nerve-fusiform cell synapses versus auditory nerve-bushy cell synapses, where GluA3 predominates; GluA4 immunogold is homogeneously distributed along both synapse types, while GluA3 is concentrated centrally at AN-BC synapses. Quantitative freeze-fracture replica immunogold labeling, GluA3-KO mice Brain structure & function High 28397107
2017 De novo variants in the SYTANLAAF motif of GluA4 transmembrane domain M3 that face the pore center are predicted by molecular modeling to disturb gating mechanism; a fourth SYTANLAAF variant reduces permeability; an extracellular domain variant interferes with monomer-monomer binding, establishing structural mechanisms for pathogenic GluA4 gain-of-function variants. Whole-exome sequencing, molecular modeling of variant positions in transmembrane domain American journal of human genetics Medium 29220673
2016 GluA4-deficient mice lack both homeostatic upregulation of glutamatergic transmission in neonatal CA3 (triggered by 15-h TTX blockade) and Hebbian weakening of AMPAR transmission in CA1 following attenuation of correlated bursting, demonstrating that GluA4 mediates both homeostatic and Hebbian plasticity mechanisms at immature hippocampal synapses. GluA4-KO mice, whole-cell electrophysiology, TTX activity blockade paradigm Journal of neurophysiology High 26961102

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy. Nature neuroscience 150 21857658
2003 Surface expression of GluR-D AMPA receptor is dependent on an interaction between its C-terminal domain and a 4.1 protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 12574408
1999 Oligomerization and ligand-binding properties of the ectodomain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluRD. The Journal of biological chemistry 79 10506139
2008 Absence seizures in C3H/HeJ and knockout mice caused by mutation of the AMPA receptor subunit Gria4. Human molecular genetics 72 18316356
1996 Characterization of the ligand-binding domains of glutamate receptor (GluR)-B and GluR-D subunits expressed in Escherichia coli as periplasmic proteins. The Journal of biological chemistry 59 8663017
2017 De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities. American journal of human genetics 53 29220673
2003 Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 45 12497607
2020 CircCBFB-mediated miR-28-5p facilitates abdominal aortic aneurysm via LYPD3 and GRIA4. Life sciences 42 32151690
1995 Purification of recombinant GluR-D glutamate receptor produced in Sf21 insect cells. European journal of biochemistry 39 8521834
2019 Genes CEP55, FOXD3, FOXF2, GNAO1, GRIA4, and KCNA5 as potential diagnostic biomarkers in colorectal cancer. BMC medical genomics 38 30987631
2016 Acoustic trauma slows AMPA receptor-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function. The Journal of physiology 30 27104476
2008 Study on GRIA2, GRIA3 and GRIA4 genes highlights a positive association between schizophrenia and GRIA3 in female patients. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 27 18163426
2017 The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells. Brain structure & function 26 28397107
2014 Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors. Proceedings of the National Academy of Sciences of the United States of America 25 24599589
1998 Disulfide bonding and cysteine accessibility in the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit GluRD. Implications for redox modulation of glutamate receptors. The Journal of biological chemistry 24 9737972
2018 Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression. Translational psychiatry 23 30287806
2013 Pain after discontinuation of morphine treatment is associated with synaptic increase of GluA4-containing AMPAR in the dorsal horn of the spinal cord. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 21 23403695
2021 GluA4 facilitates cerebellar expansion coding and enables associative memory formation. eLife 19 34219651
2016 Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses. Neuropharmacology 19 27157711
2019 GluA4-Targeted AAV Vectors Deliver Genes Selectively to Interneurons while Relying on the AAV Receptor for Entry. Molecular therapy. Methods & clinical development 18 31463334
2014 Unraveling genetic modifiers in the gria4 mouse model of absence epilepsy. PLoS genetics 18 25010494
2014 Sequential delivery of synaptic GluA1- and GluA4-containing AMPA receptors (AMPARs) by SAP97 anchored protein complexes in classical conditioning. The Journal of biological chemistry 16 24567325
2015 Ionotropic glutamate receptor GluA4 and T-type calcium channel Cav 3.1 subunits control key aspects of synaptic transmission at the mouse L5B-POm giant synapse. The European journal of neuroscience 15 26390982
2016 GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus. Journal of neurophysiology 13 26961102
2004 No genetic association between polymorphisms in the AMPA receptor subunit GluR4 gene (GRIA4) and schizophrenia in the Chinese population. Neuroscience letters 13 15450689
2009 Ethanol increases desensitization of recombinant GluR-D AMPA receptor and TARP combinations. Alcohol (Fayetteville, N.Y.) 12 19560629
2021 Role of GluA4 in the acoustic and tactile startle responses. Hearing research 11 34915397
2023 Hypermethylated GRIA4, a potential biomarker for an early non-invasive detection of metastasis of clinically known colorectal cancer. Frontiers in oncology 9 37476382
2022 Novel Heterozygous Missense Variant in GRIA4 Gene Associated With Neurodevelopmental Disorder With or Without Seizures and Gait Abnormalities. Frontiers in genetics 9 35518358
2016 Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter methylation levels are modulated at retrieval in spatial learning of the rat. Amino acids 9 27714514
2004 GluR4c, an alternative splicing isoform of GluR4, is abundantly expressed in the adult human brain. Brain research. Molecular brain research 9 15306133
2013 Genetic analysis of GRIA2 and GRIA4 genes in migraine. Headache 8 24512576
2002 Discrimination between agonists and antagonists by the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-selective glutamate receptor. A mutation analysis of the ligand-binding domain of GluR-D subunit. The Journal of biological chemistry 8 12167621
2021 Neuronal activity regulated pentraxin (narp) and GluA4 subunit of AMPA receptor may be targets for fluoxetine modulation. Metabolic brain disease 7 33528752
2017 GluA4 Dependent Plasticity Mechanisms Contribute to Developmental Synchronization of the CA3-CA1 Circuitry in the Hippocampus. Neurochemical research 7 28856535
2010 Analysis of the potential role of GluA4 carboxyl-terminus in PDZ interactions. PloS one 7 20090852
2013 Investigation of possible epistatic interactions between GRIA2 and GRIA4 variants on clinical outcomes in patients with major depressive disorder. The Journal of international medical research 6 23613500
2002 Determinants of antagonist binding at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit, GluR-D. Role of the conserved arginine 507 and glutamate 727 residues. European journal of biochemistry 6 12473122
2025 GluA4 AMPA receptor gating mechanisms and modulation by auxiliary proteins. Nature structural & molecular biology 5 40954371
2019 Stargazin and γ4 slow the channel opening and closing rates of GluA4 AMPA receptors. Scientific reports 4 31267004
2010 Cloning and characterization of glutamate receptor subunit 4 (GLUA4) and its alternatively spliced isoforms in turtle brain. Journal of molecular neuroscience : MN 3 20549383
2025 Architecture, Activation, and Conformational Plasticity in the GluA4 AMPA Receptor. bioRxiv : the preprint server for biology 2 40667226
2026 Structural basis for activation and conformational plasticity of the GluA4 AMPA receptor. Nature communications 1 41656278
2016 A parallel panning scheme used for selection of a GluA4-specific Fab targeting the ligand-binding domain. International journal of biological macromolecules 1 27402461