Affinage

Showing GRIA1 — GLUR1 is a alias.

GRIA1

Glutamate receptor 1 · UniProt P42261

Length
906 aa
Mass
101.5 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIA1 encodes GluA1 (GluR1), a subunit of AMPA-type glutamate receptors whose synaptic abundance, channel behavior, and contribution to bidirectional plasticity are governed by a dense layer of post-translational and trafficking control (PMID:12628184, PMID:18077682). Phosphorylation of the C-terminus at distinct sites integrates multiple kinase pathways: PKA phosphorylates Ser845 to raise channel open probability (reversed by calcineurin) (PMID:10627585), PKC and CaMKII act at Ser831 to increase single-channel conductance (PMID:22373567), CK2 modifies Ser579 (PMID:24712994), and PAK3 phosphorylates the site Ser863 downstream of EphB2–Cdc42 signaling (PMID:26460013); Ser845 phosphorylation is required for LTD while either Ser831 or Ser845 supports LTP, and phosphomimetic substitution lowers the LTP induction threshold (PMID:12628184, PMID:19906877, PMID:21536866). Ser845 phosphorylation controls surface residence largely by reducing GluA1 binding to the AP2 clathrin adaptor, limiting internalization (PMID:34369573). Convergent signaling routes feed these modifications, including D1 dopamine receptor/DARPP-32-cAMP/PKA (PMID:10844017), cGKII binding the GluA1 C-terminus (PMID:18031684), and a β2-adrenergic receptor complex assembled through stargazin and PSD-95 (PMID:19942860). Surface levels are further set by Nedd4-1-mediated ubiquitination at Lys868 directing post-endocytic receptors to lysosomes in a Ca2+/CaMKII-dependent manner (PMID:21148011, PMID:25660027), by S-nitrosylation at Cys875 that couples NMDAR-NO signaling to conductance, Ser831 phosphorylation and AP2-dependent endocytosis (PMID:23277581), and by C-terminal interactions with the 4.1N/actin cytoskeleton (PMID:11050113). Beyond ion conduction, the GluA1 C-tail confers a structural plasticity function permitting LTP-associated spine enlargement independent of channel activity (PMID:18077682), while the amino-terminal domain anchors receptors at the postsynaptic membrane through neuroplastin-65 to sustain LTP (PMID:33627404); cryo-EM of GluA1/TARP complexes shows that the sequence-diverse NTD forms a mobile assembly whose anchoring efficiency determines gating kinetics and synaptic signaling strength (PMID:37704721, PMID:35136046). GluA1 expression is additionally tuned at the transcriptional, translational, and mRNA-stability levels by CREB (PMID:23504989), FUS and FXR2P/FMRP (PMID:25968143, PMID:26051932), hnRNP A2/B1-driven IRES translation (PMID:33219033), and the microRNAs miR-92a and miR-501-3p that regulate homeostatic scaling and activity-dependent spine remodeling (PMID:25017011, PMID:25800054).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established the enzymatic logic of GluA1 C-terminal phosphorylation: PKA at Ser845 raises channel open probability while a parallel cAMP/PKA pathway downstream of D1/DARPP-32 selectively writes Ser845 in vivo.

    Evidence Outside-out patch clamp with purified PKA/calcineurin and S845A/S831A mutants; phospho-specific antibodies in neostriatal slices with DARPP-32 knockout mice

    PMID:10627585 PMID:10844017

    Open questions at the time
    • Did not establish which phosphatases reverse Ser845 in vivo beyond calcineurin
    • Did not separate gating effect from trafficking effect of Ser845
  2. 2000 High

    Linked the GluA1 C-terminus to the actin cytoskeleton, showing surface expression depends on a membrane-proximal 4.1N/4.1G interaction.

    Evidence Yeast two-hybrid, in vivo Co-IP, surface biotinylation, and actin disruption in heterologous cells and cortical neurons

    PMID:11050113

    Open questions at the time
    • Did not define how 4.1N binding is regulated during plasticity
    • Did not connect 4.1N anchoring to specific phosphorylation events
  3. 2003 High

    Demonstrated in vivo that Ser831/Ser845 phosphorylation is required for bidirectional plasticity and spatial memory, moving these sites from biochemical markers to physiological determinants.

    Evidence S831A/S845A double knockin mice with hippocampal LTP/LTD recordings and behavioral memory tasks

    PMID:12628184

    Open questions at the time
    • Did not resolve the individual contribution of each site
    • Did not address the channel-versus-trafficking basis of the deficit
  4. 2007 High

    Separated GluA1's structural role from its ion-channel role and identified cGKII as a Ser845 kinase coupling cGMP to surface delivery and LTP.

    Evidence Channel-dead and cytosolic C-tail constructs with two-photon spine imaging; cGKII Co-IP, in vitro kinase assay, biotinylation, and LTP recordings

    PMID:18031684 PMID:18077682

    Open questions at the time
    • Did not identify the PSD effector through which the C-tail drives spine enlargement
    • Did not establish endogenous cGKII contribution to physiological LTP
  5. 2009 High

    Resolved site-specific division of labor (Ser845 required for LTD, either site sufficient for LTP) and showed receptor-selective PKA action via a β2AR–stargazin–PSD-95 complex.

    Evidence Single-site S831A/S845A knockin electrophysiology; Co-IP and interference peptides with EPSC recordings in PFC slices

    PMID:19906877 PMID:19942860

    Open questions at the time
    • Did not define how the β2AR complex confines PKA to associated GluA1
    • Did not address whether other GPCRs use analogous scaffolds
  6. 2010 High

    Identified Nedd4-1 as the E3 ligase that ubiquitinates GluA1 C-terminal lysines after AMPA stimulation to route receptors to lysosomes, defining a degradative trafficking arm.

    Evidence Ubiquitination-deficient mutants, Nedd4-1 gain/loss-of-function, live-cell trafficking imaging, AMPA versus NMDA stimulation

    PMID:21148011

    Open questions at the time
    • Did not pinpoint the exact lysine at this stage
    • Did not define deubiquitinase counterpart
  7. 2011 High

    Provided gain-of-function evidence that S831/S845 phosphorylation is sufficient to lower the LTP threshold, complementing the loss-of-function knockins.

    Evidence S831D/S845D phosphomimetic knockin mice with multiple LTP induction protocols and biotinylation

    PMID:21536866

    Open questions at the time
    • Phosphomimetics do not fully reproduce dynamic phosphorylation
    • Did not resolve relative contribution of each pseudo-phosphorylated site
  8. 2012 High

    Expanded the modification map: PKC at Ser831 raises conductance, and NMDAR-driven S-nitrosylation at Cys875 couples NO signaling to conductance, Ser831 phosphorylation, and AP2-dependent endocytosis.

    Evidence Patch clamp with purified PKC and S831A in GluA1+stargazin; C875 mutagenesis, single-channel recording, AP2 Co-IP, endocytosis assays

    PMID:22373567 PMID:23277581

    Open questions at the time
    • Did not establish stoichiometry between nitrosylation and phosphorylation in vivo
    • Did not identify the nitrosylase/denitrosylase enzymes
  9. 2015 High

    Mapped activity-dependent ubiquitination to Lys868 on plasma-membrane receptors and identified PAK3 (downstream of EphB2-Cdc42) as a kinase writing the new Ser863 site, broadening the trafficking control network.

    Evidence Site mutagenesis with Ca2+ channel/CaMKII inhibitors and endosome assays; in vitro PAK3 kinase assay, EphB2 Co-IP, PAK3 RNAi and inhibition with surface biotinylation

    PMID:25660027 PMID:26460013

    Open questions at the time
    • Did not identify the E3 ligase acting at Lys868 in this context
    • Did not define the phosphatase removing Ser863
  10. 2015 High

    Established that GluA1 abundance is set translationally and post-transcriptionally by RNA-binding proteins and microRNAs, linking GluA1 expression to homeostatic scaling and neurodevelopmental behavior.

    Evidence FUS and FXR2P/FMRP knockdown/knockout with RIP, poly(A) and surface assays, mEPSC, and behavioral rescue; miR-92a 3'UTR reporter and homeostatic scaling assays

    PMID:25017011 PMID:25968143 PMID:26051932

    Open questions at the time
    • Did not integrate these RNA-level controls with synaptic phosphorylation events
    • Did not establish in vivo hierarchy among the regulators
  11. 2021 High

    Defined an N-terminal-domain anchoring mechanism via neuroplastin-65 required for LTP maintenance, and refined Ser845's role as predominantly anti-internalization by reducing AP2 binding.

    Evidence CRISPR single-neuron AMPAR replacement with GluA1 ATD-Np65 binding assays and LTP; FRAP with S845 phosphomutants and AP2 Co-IP

    PMID:33627404 PMID:34369573

    Open questions at the time
    • Did not resolve how Np65 anchoring is dynamically engaged during plasticity
    • Did not reconcile structural anchoring with C-tail-driven spine enlargement
  12. 2023 High

    Provided structural mechanism: cryo-EM of GluA1/TARP complexes showed the mobile sequence-diverse NTD assembly governs gating transitions and that NTD anchoring efficiency dictates synaptic signaling strength.

    Evidence Cryo-EM of resting/open/desensitized GluA1/γ3 and GluA1/2-γ8 states with GluA2 F231A mutagenesis and electrophysiology

    PMID:35136046 PMID:37704721

    Open questions at the time
    • Did not capture phosphorylated or ubiquitinated receptor states structurally
    • Did not visualize NTD engagement with synaptic adhesion partners such as Np65

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many parallel inputs—C-terminal phosphorylation/ubiquitination/nitrosylation, NTD anchoring, cytoskeletal and scaffold interactions, and RNA-level expression control—are temporally coordinated at a single synapse during plasticity remains unresolved.
  • No integrated model linking modification timing to trafficking step
  • Structural basis of regulated states not determined
  • In vivo hierarchy among redundant kinases and RNA regulators unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 5 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3
Partners
AP2CACNG2DLG1DLG4EPB41L1NEDD4NPTNPRKG2
Complex memberships
GluA1-SAP97-AKAP79/150-p85S6K complexGluA1-TARP (stargazin/γ3/γ8) AMPA receptor complexβ2AR-stargazin-PSD-95 signaling complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Phosphorylation of GluR1 at Ser831 and Ser845 is required for LTP and LTD expression and spatial memory retention; knockin mice with alanine substitutions at both sites show deficits in bidirectional synaptic plasticity and spatial learning. Knockin mutagenesis (S831A/S845A double phosphomutant mice), hippocampal slice electrophysiology (LTP/LTD), behavioral memory tasks Cell High 12628184
2009 The S845 phosphorylation site on GluR1 is specifically required for LTD expression in CA1, while S831 alone is dispensable; either S831 or S845 alone can support LTP. Single-site knockin mice (S831A or S845A), hippocampal slice electrophysiology (LTP/LTD at Schaffer collateral-CA1 synapses) Journal of neurophysiology High 19906877
2000 PKA phosphorylation of GluR1 at Ser845 increases the peak open probability of homomeric GluR1 AMPA receptors without altering single-channel conductance, unitary current, or macroscopic response waveform; calcineurin reverses this effect. The S845A mutation abolishes the PKA-induced increase in open probability. Outside-out patch clamp recordings, purified PKA catalytic subunit and calcineurin inclusion in pipette, site-directed mutagenesis (S845A, S831A) in recombinant GluR1(flip) receptors The Journal of neuroscience High 10627585
2000 GluR1 interacts with protein 4.1N and 4.1G via the membrane-proximal region of the GluR1 C-terminus; disruption of this interaction or actin filaments reduces GluR1 surface expression in heterologous cells and reduces surface AMPA receptors in cortical neurons, linking GluR1 to the actin cytoskeleton. Yeast two-hybrid, heterologous cell co-expression, in vivo co-immunoprecipitation, immunofluorescence co-localization, actin disruption experiments (latrunculin), surface biotinylation The Journal of neuroscience High 11050113
2000 D1 dopamine receptor activation increases GluR1 phosphorylation at Ser845 (via cAMP/PKA) but not at Ser831 in neostriatum; psychostimulants cocaine and methamphetamine also increase Ser845 phosphorylation in vivo; these effects are attenuated in DARPP-32 knockout mice, placing DARPP-32 upstream of GluR1 Ser845 phosphorylation. Phosphorylation site-specific antibodies, neostriatal slices, in vivo drug treatment, DARPP-32 knockout mice The Journal of neuroscience High 10844017
2007 Synaptic insertion of GluR1 is required (but not sufficient) to permit stable spine enlargement during LTP; this structural function is mediated through the GluR1 C-terminal domain independently of ion channel activity, as a cytosolic C-tail fragment alone is sufficient to permit spine enlargement when driven to the postsynaptic density. Hippocampal slice cultures and in vivo LTP induction, GluR1 mutants (ion channel dead), recombinant C-tail fragment expression, two-photon imaging of spine morphology The Journal of neuroscience High 18077682
2007 cGMP-dependent protein kinase II (cGKII) binds the GluR1 C-terminal domain adjacent to the kinase catalytic site; cGKII activation by cGMP increases this interaction and phosphorylates GluR1 at Ser845, increasing surface AMPAR expression at extrasynaptic sites; inhibition of cGKII blocks LTP in hippocampal slices. Co-immunoprecipitation from brain, pulldown assays, in vitro kinase assay, surface biotinylation, hippocampal slice LTP recordings, cGKII inhibitor experiments Neuron High 18031684
2010 AMPA-induced (but not NMDA-induced) ubiquitination of GluA1 at C-terminal lysines by the E3 ligase Nedd4-1 mediates GluA1 internalization and trafficking to lysosomes; a ubiquitination-deficient GluA1 mutant (C-terminal lysine mutations) fails to be internalized to lysosomes in response to AMPA. Ubiquitination-deficient GluA1 mutants (C-terminal lysine mutations), Nedd4-1 overexpression/RNAi knockdown, live-cell imaging of receptor trafficking, AMPA vs NMDA agonist stimulation The Journal of neuroscience High 21148011
2015 Activity-dependent ubiquitination of GluA1 at Lys-868 (and GluA2 at Lys-870/Lys-882) occurs exclusively on plasma membrane receptors post-endocytosis; this ubiquitination is Ca2+-dependent, requires L-type VGCCs and CaMKII, and controls intracellular trafficking to late endosomes/lysosomes for degradation rather than endocytosis per se. Site-directed mutagenesis of ubiquitination sites, ubiquitination assays in cultured neurons, Ca2+ channel/CaMKII inhibitors, late endosome trafficking assays, surface biotinylation Cell reports High 25660027
2009 The beta2-adrenergic receptor (β2AR) forms a supramolecular signaling complex with GluR1 through stargazin and PSD-95; PKA in this complex selectively phosphorylates GluR1 associated with β2AR upon β2AR stimulation, increasing GluR1 surface expression at postsynaptic sites and augmenting EPSC amplitudes in PFC slices. Co-immunoprecipitation, interference peptides disrupting β2AR-GluR1 association, surface biotinylation, electrophysiology (EPSC/mEPSC recordings in PFC slices) The EMBO journal High 19942860
2012 S-nitrosylation of GluA1 at Cys875, downstream of NMDA receptor activation and NO production, enhances phosphorylation at Ser831, increases single-channel conductance, and promotes endocytosis by increasing GluA1 binding to the AP2 endocytic adaptor. S-nitrosylation site mapping (C875), site-directed mutagenesis, outside-out patch clamp single-channel recordings, AP2 co-immunoprecipitation, endocytosis assays Proceedings of the National Academy of Sciences of the United States of America High 23277581
2012 PKC phosphorylates GluA1 at Ser831 to increase AMPA receptor single-channel conductance; the S831A mutation blocks this PKC-induced conductance increase in GluA1 receptors co-expressed with stargazin. Outside-out patch clamp in HEK293T cells expressing GluA1 + stargazin, purified PKC catalytic subunit, S831A mutagenesis Channels (Austin, Tex.) High 22373567
2015 PAK3, downstream of EphB2-Cdc42 signaling via Zizimin1 (a GEF for Cdc42), phosphorylates GluA1 at a previously unknown site Ser863 in vitro; loss or pharmacological inhibition of PAK3 disrupts activity-dependent S863 phosphorylation in cortical neurons, reducing GluA1 surface trafficking. In vitro kinase assay (PAK3 phosphorylation of GluA1), EphB2 co-immunoprecipitation, RNAi knockdown of PAK3, pharmacological PAK inhibition, surface biotinylation in cortical neurons Proceedings of the National Academy of Sciences of the United States of America High 26460013
2011 Phosphomimetic knockin mice (GluA1 S831D/S845D) show normal basal synaptic transmission but a lowered threshold for LTP induction (10-Hz and STDP protocols that are subthreshold in WT induce LTP), indicating that GluA1 phosphorylation at S831 and S845 is sufficient to lower the LTP induction threshold. Knockin phosphomimetic mice, hippocampal slice electrophysiology with multiple LTP induction protocols (theta-burst, 10-Hz, STDP), surface biotinylation Proceedings of the National Academy of Sciences of the United States of America High 21536866
2021 The amino-terminal domain (ATD) of GluA1 is required for LTP maintenance; GluA1 ATD directly interacts with the cell adhesion molecule neuroplastin-65 (Np65), and deletion of Np65 or disruption of GluA1-Np65 binding severely impairs LTP maintenance, revealing an anchoring mechanism for AMPARs at the postsynaptic membrane. CRISPR/Cas9 deletion of endogenous AMPARs with single-neuron replacement by mutant forms, direct binding assay (GluA1 ATD–Np65 interaction), Np65 knockout, hippocampal slice LTP recordings Proceedings of the National Academy of Sciences of the United States of America High 33627404
2023 Cryo-EM structures of the GluA1 homotetramer fully occupied with TARPγ3 (GluA1/γ3) in resting and open states reveal that the sequence-diverse N-terminal domains (NTDs) create a highly mobile assembly enabling domain swapping and subunit re-alignments in the LBD tier that are pronounced in desensitized states; these transitions underlie GluA1's unique kinetic properties. A GluA2 F231A mutant that increases NTD dynamics phenocopies GluA1 behaviour and shows reduced synaptic responses, demonstrating that NTD anchoring function determines synaptic signalling efficiency. Cryo-electron microscopy structure determination (resting and open-state GluA1/γ3), site-directed mutagenesis (GluA2 F231A), electrophysiology Nature High 37704721
2022 Cryo-EM structures of GluA1/2-TARPγ8 in open and desensitized states reveal state-selective engagement of LBDs by the TARPγ8 β1 loop, showing how γ8 stabilizes specific gating states; TARPs alter channel rectification by interacting with the pore helix of the selectivity filter; the Q/R-editing site couples channel constriction at the filter entrance to the gate. Cryo-electron microscopy (3.5 Å resolution GluA1/2-γ8 open and desensitized state structures), electrophysiological validation Nature communications High 35136046
2004 The lurcher mutation in GluR1 primarily increases the receptor's affinity for glutamate and reduces desensitization at nanomolar glutamate concentrations, making channel opening and desensitization rate strongly dependent on subunit occupancy; GluR1Lc channels show little or no constitutive activity at ambient glutamate levels, contrary to previous reports. Kinetic analysis of GluR1Lc channels: leak current measurement with NBQX blockade, single-channel recordings, glutamate concentration-response analysis in HEK cells The Journal of neuroscience High 15163686
2001 The GluR1 promoter lacks TATA and CAAT elements but contains two Sp1 binding sites; neuronal specificity resides in enhancer regions (-1395 to -743 and -253 to -48); the -253 to -202 region contains CRE sites and a glial silencing element; a 64-bp GA repeat upstream of transcription start sites increases activity, and an N-box-containing region reduces it. Promoter deletion analysis with luciferase reporter in primary cortical neurons and glia, immunocytochemistry, gel-shift assays (Sp1/CREB binding) The Journal of biological chemistry Medium 11340067
2005 SGK3 (serum- and glucocorticoid-inducible kinase 3), downstream of PI3-kinase, increases GluR1 protein abundance in the cell membrane in Xenopus oocytes; hippocampal GluR1 abundance is significantly reduced in SGK3 knockout mice. Xenopus oocyte expression system with electrophysiology, SGK3 knockout mice with Western blotting, in situ hybridization The Journal of physiology Medium 15774536
2012 SGK3 promotes GluR1 plasma membrane delivery via a RAB11-dependent, PIKfyve/PI(3,5)P2-dependent trafficking pathway; PIKfyve inhibition reduces basal synaptic activity in CA1 and shifts GluA1 expression away from synapses in hippocampal neurons. Xenopus oocyte electrophysiology, dominant-negative RAB11, PIKfyve inhibitor (YM201636) in hippocampal slices and neurons, in vitro kinase assay (SGK3 phosphorylation of PIKfyve) PloS one Medium 22470488
2012 JNK1 phosphorylates the transcriptional repressor Hes-1 at Ser263, stabilizing Hes-1 protein, which suppresses GluR1 promoter activity by binding the N-box and blocking Mash1/E47 from binding the E-box; this JNK1-Hes-1 pathway inhibits AMPA-evoked calcium influx in cortical neurons. In vitro kinase assay (JNK1 phosphorylation of Hes-1), promoter reporter assays, site-directed mutagenesis (N-box/E-box), overexpression/knockdown in rat cortical neurons, Ca2+ imaging The Journal of neuroscience Medium 22302822
2014 Casein kinase 2 (CK2) phosphorylates GluA1 at Ser579 within the intracellular loop1 region; knockdown of CK2 regulatory subunit CK2β reduces GluA1 surface expression, and expression of S579 phosphodeficient GluA1 in hippocampal neurons reduces surface expression. In vitro phosphorylation assay (panel of purified kinases), CK2β shRNA knockdown, S579A/phosphodeficient mutant expression, surface biotinylation in hippocampal neurons The European journal of neuroscience Medium 24712994
2015 FUS RNA-binding protein binds GluA1 mRNA near the 3' terminus and controls poly(A) tail maintenance to regulate GluA1 mRNA stability; FUS depletion downregulates GluA1 protein, reduces miniature EPSC amplitude in vitro and in vivo, impairs dendritic spine maturation, and causes hyperactivity/social interaction defects partially rescued by GluA1 reintroduction. FUS knockdown (siRNA/shRNA), RNA immunoprecipitation (FUS–GluA1 mRNA interaction), poly(A) tail assays, miniature EPSC recordings, spine morphology analysis, behavioral assays with GluA1 rescue Nature communications High 25968143
2015 FXR2P binds and stabilizes GluA1 mRNA to enhance GluA1 protein expression, while FMRP promotes GluA1 membrane delivery; the two fragile X proteins thus regulate GluA1 via distinct mechanisms that additively promote neuronal maturation. FXR2P/FMRP knockout mice, RNA immunoprecipitation (FXR2P–GluA1 mRNA), surface biotinylation of GluA1, dendritic morphology analysis, behavioral learning assays Cell reports High 26051932
2020 HNRNP A2/B1 interacts with an IRES in the GluA1 mRNA 5'UTR and mediates cap-independent (IRES-driven) translation of GluA1; BDNF stimulation upregulates HNRNP A2/B1 to increase IRES-mediated GluA1 translation and dendritic spine density; neurons lacking hnRNP A2/B1 show decreased BDNF-induced GluA1 expression. IRES reporter assays, RNA pulldown (hnRNP A2/B1–GluA1 mRNA interaction), hnRNP A2/B1 knockdown/overexpression, BDNF stimulation, spine density quantification Science advances Medium 33219033
2014 miR-92a represses GluA1 translation by binding the 3'UTR of GluA1 mRNA and is downregulated during activity blockade (TTX+AP5); blocking the miR-92a seed region in GluA1 or overexpressing miR-92a prevents homeostatic scaling up of synaptic GluA1-containing AMPARs. miR-92a 3'UTR reporter assay, TTX/AP5 activity blockade in hippocampal neurons, GluA1 3'UTR seed region deletion, miR-92a overexpression, surface AMPAR expression analysis Nature neuroscience High 25017011
2015 miR-501-3p targets the 3'UTR of GluA1 mRNA and suppresses GluA1 expression; miR-501-3p is upregulated in dendrites via NMDAR GluN2A subunit activation, and this upregulation is required for NMDA-induced suppression of GluA1 expression and long-lasting dendritic spine remodeling. Deep sequencing of 3'UTR pulldown miRNAs, 3'UTR luciferase reporter, miR-501-3p overexpression/inhibition, GluN2A-specific NMDAR blockers, spine morphology imaging The Journal of cell biology Medium 25800054
2015 TNF-α–driven TRAF2-TNIK association phosphorylates GluR1 and drives GluR1-containing AMPA receptor trafficking toward the plasma membrane in spinal dorsal horn neurons; Fbxo3-dependent ubiquitination of Fbxl2 regulates TRAF2 levels to modulate this TNIK/GluR1 cascade, contributing to neuropathic allodynia. Spinal nerve ligation model, TNIK-GluR1 co-immunoprecipitation, GluR1 phosphorylation assays, siRNA knockdown of TNIK/Fbxo3, intrathecal drug administration, behavioral allodynia assays The Journal of neuroscience Medium 26674878
2021 Phosphorylation of GluA1 Ser845 reduces binding of the clathrin adaptor AP2 to GluA1, thereby reducing clathrin-mediated internalization of AMPARs; FRAP experiments show S845 phosphorylation predominantly acts on receptor internalization rather than forward trafficking during synaptic plasticity. FRAP (fluorescence recovery after photobleaching), AP2-GluA1 co-immunoprecipitation, S845 phosphomutants, synaptic plasticity induction (LTP, synaptic upscaling) Journal of cell science Medium 34369573
2002 GluR1 AMPA receptor subunit overexpression in spinal motor neurons promotes dendritic arborization and filopodial outgrowth in a manner dependent on the Q/R editing site of GluR1 (which determines Ca2+ permeability); these effects are not blocked by NMDA receptor antagonism, suggesting a GluR1-specific, NMDAR-independent mechanism. Viral overexpression of GluR1 (Q vs R variants) in rat spinal motor neurons, quantitative dendritic morphometry, NMDA receptor blockade The Journal of neuroscience Medium 12223558
2009 GluA1-independent LTP at CA3-CA1 synapses has a more sustained component induced via GluN2B-containing NMDARs, neuronal nitric oxide synthase, and PKC (regulators of GluA2 surface expression); this is distinct from the rapidly decaying GluA1-dependent LTP component. Gria1-/- mice, theta-burst LTP induction, nNOS inhibitors, PKC inhibitors, GluN2B antagonists, hippocampal slice electrophysiology The European journal of neuroscience Medium 19302150
2015 CPT1C (carnitine palmitoyltransferase 1C) interacts with GluA1 intracellularly and enhances surface expression of GluA1-containing AMPARs; the palmitoylable residue C585 of GluA1 is required for CPT1C-mediated trafficking enhancement, although CPT1C does not alter GluA1 palmitoylation state. Co-immunoprecipitation in heterologous cells, whole-cell patch clamp, surface biotinylation, C585 mutagenesis, co-localization imaging Frontiers in cellular neuroscience Medium 25698923
2018 p85S6K isoform (but not p70S6K) is enriched in postsynaptic densities, interacts with GluA1 through SAP97 and AKAP79/150, and directly phosphorylates GluA1 at Ser845, thereby sustaining synaptic GluA1 levels and spine density; p85S6K is decreased in AD brain synaptosomal fractions, and its overexpression rescues synaptic deficits in AD model mice. Subcellular fractionation, Co-IP (p85S6K–GluA1 via SAP97/AKAP79/150), in vitro kinase assay (p85S6K→GluA1 Ser845), in situ proximity ligation assay, knockdown/overexpression in AD mice, behavioral and spine density analyses Translational neurodegeneration Medium 36624510
2002 CXCR2 chemokine receptor co-expressed with GluR1 in HEK cells increases GluR1 apparent affinity for glutamate, channel open probability, and binding site cooperativity upon CXCL2 stimulation; C-terminal deletion of GluR1 abolishes this affinity change, implicating the C-terminus in CXCR2-GluR1 functional coupling. HEK cell co-expression electrophysiology, CXCL2 stimulation, GluR1 C-terminal deletion mutants, spontaneous EPSC recordings in cerebellar neurons Journal of neuroimmunology Low 12161022
2017 R/G editing in the GluA2R flop isoform accelerates the rate of channel opening and desensitization in GluA1/2R heteromeric channels when GluA1 is in the flop form, but has no effect on channel-closing rate or EC50; GluA1 flip/flop status modulates the impact of GluA2 R/G editing on channel kinetics. Laser-pulse photolysis combined with whole-cell recording, systematic comparison of R/G editing × flip/flop variants in heteromeric GluA1/2R channels Scientific reports Medium 29057893
2013 CREB is required for basal synaptic maintenance of GluA1 within the postsynaptic density and for learning-induced increases in synaptic GluA1 and pSer845-GluA1; dominant-negative CREB reduces GluA1 in PSDs, decreases LTP, increases LTD, and blocks contextual fear conditioning-driven GluA1 trafficking to the PSD. Conditional dominant-negative CREB transgenic mice (CREBS133A), PSD fractionation, Western blotting with phospho-specific antibodies, hippocampal electrophysiology (mEPSC, LTP, LTD), contextual fear conditioning Hippocampus Medium 23504989
1997 25-40% of GluR1 (as well as GluR2 and GluR4) protein is located at the plasma membrane in stably transfected BHK cells; the surface-localized fraction corresponds to the fully glycosylated upper band on Western blots, indicating that complete glycosylation is required for GluR subunit trafficking to the cell surface. BS3 crosslinking, surface biotinylation/neutravidin precipitation, [3H]AMPA binding, glycopeptidase F treatment, Western blotting in stably transfected BHK cells Journal of neurochemistry Medium 9003049

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 649 12628184
2000 Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase. The Journal of neuroscience : the official journal of the Society for Neuroscience 499 10627585
2000 Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. The Journal of neuroscience : the official journal of the Society for Neuroscience 245 11050113
2000 Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 234 10844017
2009 Specific roles of AMPA receptor subunit GluR1 (GluA1) phosphorylation sites in regulating synaptic plasticity in the CA1 region of hippocampus. Journal of neurophysiology 221 19906877
2002 Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Molecular and cellular neurosciences 214 11860268
2007 GluR1 links structural and functional plasticity at excitatory synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 186 18077682
2010 Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience 162 21148011
2007 A GluR1-cGKII interaction regulates AMPA receptor trafficking. Neuron 145 18031684
1998 Expression of NMDAR1, GluR1, GluR7, and KA1 glutamate receptor mRNAs is decreased in frontal cortex of "neuroleptic-free" schizophrenics: evidence on reversible up-regulation by typical neuroleptics. Journal of neurochemistry 145 9832144
1993 Expression of glutamate receptor genes in the mammalian retina: the localization of GluR1 through GluR7 mRNAs. The Journal of neuroscience : the official journal of the Society for Neuroscience 137 8478682
2019 Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function. Molecular psychiatry 130 30894661
2015 FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1 mRNA stabilization. Nature communications 125 25968143
2008 The role of the GluR-A (GluR1) AMPA receptor subunit in learning and memory. Progress in brain research 113 18394473
2002 D1 dopamine receptor stimulation increases GluR1 surface expression in nucleus accumbens neurons. Journal of neurochemistry 112 12390532
2015 Activity-Dependent Ubiquitination of GluA1 and GluA2 Regulates AMPA Receptor Intracellular Sorting and Degradation. Cell reports 108 25660027
1992 Differential expression of glutamate receptor genes (GluR1-5) in the rat retina. Visual neuroscience 106 1310870
2009 Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling. The EMBO journal 91 19942860
2002 D(1) dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures. Journal of neurochemistry 84 12065610
2006 The role of nitric oxide and GluR1 in presynaptic and postsynaptic components of neocortical potentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 16837587
2008 The role of hippocampal GluR1 and GluR2 receptors in manic-like behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 18171924
2014 What causes aberrant salience in schizophrenia? A role for impaired short-term habituation and the GRIA1 (GluA1) AMPA receptor subunit. Molecular psychiatry 77 25224260
2012 S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis. Proceedings of the National Academy of Sciences of the United States of America 75 23277581
2010 Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity. Clinical pharmacology and therapeutics 73 20592726
2008 Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation. Journal of neuro-oncology 73 18317690
2003 Selective disruption of stimulus-reward learning in glutamate receptor gria1 knock-out mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 12574434
2002 The AMPA receptor subunit GluR1 regulates dendritic architecture of motor neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 12223558
2009 Induction and expression of GluA1 (GluR-A)-independent LTP in the hippocampus. The European journal of neuroscience 68 19302150
2013 PDE10 inhibition increases GluA1 and CREB phosphorylation and improves spatial and recognition memories in a Huntington's disease mouse model. Hippocampus 67 23576401
2011 Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor. Proceedings of the National Academy of Sciences of the United States of America 67 21536866
2015 Fragile X Proteins FMRP and FXR2P Control Synaptic GluA1 Expression and Neuronal Maturation via Distinct Mechanisms. Cell reports 66 26051932
2010 Enhancement of AMPA currents and GluR1 membrane expression through PKA-coupled adenosine A(2A) receptors. Hippocampus 66 21080412
2008 Role of GluR1 expression in nucleus accumbens neurons in cocaine sensitization and cocaine-seeking behavior. The European journal of neuroscience 65 18430032
2014 miR-92a regulates expression of synaptic GluA1-containing AMPA receptors during homeostatic scaling. Nature neuroscience 63 25017011
2015 Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 61 26460013
2019 Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1. Translational psychiatry 58 31000699
2004 Effects of the lurcher mutation on GluR1 desensitization and activation kinetics. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 15163686
1997 Surface expression of the AMPA receptor subunits GluR1, GluR2, and GluR4 in stably transfected baby hamster kidney cells. Journal of neurochemistry 57 9003049
2015 miR-501-3p mediates the activity-dependent regulation of the expression of AMPA receptor subunit GluA1. The Journal of cell biology 56 25800054
2013 CREB is necessary for synaptic maintenance and learning-induced changes of the AMPA receptor GluA1 subunit. Hippocampus 52 23504989
2020 Emerging role of AMPA receptor subunit GluA1 in synaptic plasticity: Implications for Alzheimer's disease. Cell proliferation 51 33188547
1998 Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus. The European journal of neuroscience 47 9751141
2021 The amino-terminal domain of GluA1 mediates LTP maintenance via interaction with neuroplastin-65. Proceedings of the National Academy of Sciences of the United States of America 45 33627404
2012 PKC phosphorylates GluA1-Ser831 to enhance AMPA receptor conductance. Channels (Austin, Tex.) 45 22373567
2004 Effects of deletion of gria1 or gria2 genes encoding glutamatergic AMPA-receptor subunits on place preference conditioning in mice. Psychopharmacology 45 15619119
2002 Chemokine receptor CXCR2 regulates the functional properties of AMPA-type glutamate receptor GluR1 in HEK cells. Journal of neuroimmunology 45 12161022
2000 A high GluR1 : GluR2 expression ratio is correlated with expression of Ca2+-binding proteins in rat forebrain neurons. The European journal of neuroscience 45 10971623
2022 Identification and functional evaluation of GRIA1 missense and truncation variants in individuals with ID: An emerging neurodevelopmental syndrome. American journal of human genetics 43 35675825
2011 AMPA receptor subunit GluR1 (GluA1) serine-845 site is involved in synaptic depression but not in spine shrinkage associated with chemical long-term depression. Journal of neurophysiology 42 21307330
2007 Elevated GRIA1 mRNA expression in Layer II/III and V pyramidal cells of the DLPFC in schizophrenia. Schizophrenia research 42 17942280
2018 Hyperammonemia alters membrane expression of GluA1 and GluA2 subunits of AMPA receptors in hippocampus by enhancing activation of the IL-1 receptor: underlying mechanisms. Journal of neuroinflammation 41 29422059
2014 Impaired path integration and grid cell spatial periodicity in mice lacking GluA1-containing AMPA receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 24790195
2006 Glutamate AMPA receptor subunit 1 gene (GRIA1) and DSM-IV-TR schizophrenia: a pilot case-control association study in an Italian sample. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 41 16526023
2001 Functional organization of the GluR1 glutamate receptor promoter. The Journal of biological chemistry 41 11340067
2016 Differential regulation of GluA1 expression by ketamine and memantine. Behavioural brain research 40 27599619
2011 Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory. Learning & memory (Cold Spring Harbor, N.Y.) 40 21378100
2021 GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases. Neuropharmacology 39 34274350
2011 Expression of the AMPA Receptor Subunits GluR1 and GluR2 is Associated with Granule Cell Maturation in the Dentate Gyrus. Frontiers in neuroscience 39 21927594
2010 Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice. The European journal of neuroscience 39 21073553
2023 Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor. Nature 38 37704721
2017 Altered GluA1 (Gria1) Function and Accumbal Synaptic Plasticity in the ClockΔ19 Model of Bipolar Mania. Biological psychiatry 38 28780133
2008 Differential regulation of dendrite complexity by AMPA receptor subunits GluR1 and GluR2 in motor neurons. Developmental neurobiology 37 18000827
2022 Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature communications 36 35136046
2015 Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 26674878
2013 The role of GluA1 in central nervous system disorders. Reviews in the neurosciences 35 24077616
2010 Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility. BMC medical genetics 35 20579352
2015 AMPAR interacting protein CPT1C enhances surface expression of GluA1-containing receptors. Frontiers in cellular neuroscience 33 25698923
2018 SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury. Frontiers in cellular neuroscience 32 29449802
2018 Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to neuropsychiatric disorders. Translational psychiatry 32 30108203
2017 Regulation of Fear Extinction in the Basolateral Amygdala by Dopamine D2 Receptors Accompanied by Altered GluR1, GluR1-Ser845 and NR2B Levels. Frontiers in behavioral neuroscience 31 28676746
2014 Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of GluA1-subunit deficient mice. PloS one 30 24932798
2005 Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3. The Journal of physiology 30 15774536
2018 GSK3β activity alleviates epileptogenesis and limits GluA1 phosphorylation. EBioMedicine 29 30502054
2014 Phosphorylation of the AMPA receptor GluA1 subunit regulates memory load capacity. Brain structure & function 29 25381005
2012 JNK1 inhibits GluR1 expression and GluR1-mediated calcium influx through phosphorylation and stabilization of Hes-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 22302822
2021 Phosphorylation of the AMPA receptor subunit GluA1 regulates clathrin-mediated receptor internalization. Journal of cell science 28 34369573
2019 Tau inhibits PKA by nuclear proteasome-dependent PKAR2α elevation with suppressed CREB/GluA1 phosphorylation. Aging cell 28 31668016
2013 Surgical incision induces phosphorylation of AMPA receptor GluR1 subunits at Serine-831 sites and GluR1 trafficking in spinal cord dorsal horn via a protein kinase Cγ-dependent mechanism. Neuroscience 28 23470774
2018 IL-1β suppresses cLTP-induced surface expression of GluA1 and actin polymerization via ceramide-mediated Src activation. Journal of neuroinflammation 27 29712570
2009 Polymorphisms in the GRIA1 gene region in psychotic bipolar disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 27 18484081
2022 (2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models. Neurobiology of stress 25 36532380
2021 Deletion of AMPA receptor GluA1 subunit gene (Gria1) causes circadian rhythm disruption and aberrant responses to environmental cues. Translational psychiatry 25 34782594
2018 AMPA receptor GluA1 Ser831 phosphorylation is critical for nitroglycerin-induced migraine-like pain. Neuropharmacology 25 29486167
2014 Casein kinase 2 phosphorylates GluA1 and regulates its surface expression. The European journal of neuroscience 25 24712994
2018 M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 29509512
2012 Identification of a novel signaling pathway and its relevance for GluA1 recycling. PloS one 24 22470488
2017 R/G editing in GluA2Rflop modulates the functional difference between GluA1 flip and flop variants in GluA1/2R heteromeric channels. Scientific reports 23 29057893
2015 Polymorphisms in GRIA1 gene are a risk factor for asparaginase hypersensitivity during the treatment of childhood acute lymphoblastic leukemia. Leukemia & lymphoma 23 25697915
2015 A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 26149358
2011 Odor preference learning and memory modify GluA1 phosphorylation and GluA1 distribution in the neonate rat olfactory bulb: testing the AMPA receptor hypothesis in an appetitive learning model. Learning & memory (Cold Spring Harbor, N.Y.) 23 21498562
2008 Protein kinase C-dependent and independent signaling pathways regulate synaptic GluR1 and GluR4 AMPAR subunits during in vitro classical conditioning. Neuroscience 23 18809472
2023 p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer's disease. Translational neurodegeneration 22 36624510
2016 Hippocampal GluA1 expression in Gria1-/- mice only partially restores spatial memory performance deficits. Neurobiology of learning and memory 22 27417577
2015 CaMKIIα-GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking. Alcoholism, clinical and experimental research 22 26247621
2013 Acute BDNF treatment upregulates GluR1-SAP97 and GluR2-GRIP1 interactions: implications for sustained AMPA receptor expression. PloS one 22 23460828
2021 Inhibition of AKT/GSK3β/CREB Pathway Improves the Responsiveness to AMPA Receptor Antagonists by Regulating GRIA1 Surface Expression in Chronic Epilepsy Rats. Biomedicines 21 33919872
2020 BDNF-induced local translation of GluA1 is regulated by HNRNP A2/B1. Science advances 21 33219033
2013 Circuit mechanisms of GluA1-dependent spatial working memory. Hippocampus 21 23929622
2019 Yy1 regulates Senp1 contributing to AMPA receptor GluR1 expression following neuronal depolarization. Journal of biomedical science 19 31629407
2013 Identification of an ionotropic glutamate receptor AMPA1/GRIA1 polymorphism in crossbred beef cows differing in fertility. Journal of animal science 19 23478821

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