Affinage

DLG4

Disks large homolog 4 · UniProt P78352

Length
724 aa
Mass
80.5 kDa
Annotated
2026-04-28
100 papers in source corpus 63 papers cited in narrative 63 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DLG4 (PSD-95) is the master scaffolding protein of excitatory postsynaptic densities, organizing glutamate receptors, ion channels, adhesion molecules, and signaling enzymes into a membrane-proximal complex that controls synaptic strength, plasticity, and synapse maturation. Its three PDZ domains recruit distinct partners—NMDA receptors and K+ channels (PDZ1/2), neuroligins and CRIPT (PDZ3)—while the catalytically inactive guanylate kinase domain binds phosphorylated SAPAPs and MAP1a, and the SH3-GK module anchors AKAP150/calcineurin and positions hippocalcin for NMDAR endocytosis (PMID:9278515, PMID:9115257, PMID:7867790, PMID:19169250, PMID:29281827). Dual palmitoylation at Cys3/Cys5 by DHHC2 (and reversed by ABHD17 thioesterases) drives a compact-to-extended conformational switch required for membrane insertion, lipid-raft targeting, and selective association with AMPA receptors via TARPs; this palmitoylation is competitively inhibited by Ca²⁺/calmodulin binding and S-nitrosylation at the same residues, providing activity-dependent mechanisms for PSD-95 release during LTD and homeostatic scaling (PMID:27956638, PMID:19596852, PMID:27307232, PMID:24705785, PMID:21745643). PSD-95 abundance at synapses is further regulated by α-actinin anchoring, ephrin-B3 stabilization, Src/Fyn and c-Abl tyrosine phosphorylation, Cdk5-gated Mdm2 ubiquitination, calpain cleavage, FMRP/miR-125a translational control, and PTBP1/2-dependent alternative splicing that gates developmental onset of expression (PMID:29429936, PMID:26479588, PMID:18721130, PMID:20220006, PMID:21849563, PMID:10825658, PMID:21658607, PMID:22246437).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Establishing that the GK domain of PSD-95 is catalytically dead resolved a paradox—a kinase-homology domain in a scaffolding protein—and recast the GK domain as a protein-interaction module, opening the search for its binding partners.

    Evidence In vitro nucleotide binding and enzymatic assays with purified GK domain

    PMID:7867790

    Open questions at the time
    • Identity of GK-binding partners unknown at this point
    • No structural basis for how GK lost catalysis
  2. 1996 High

    Immunogold EM localization of PSD-95 exclusively to the postsynaptic density, combined with the demonstration that PDZ domains cluster K+ channels at the surface, established PSD-95 as a postsynaptic scaffolding protein that organizes ion channel distribution.

    Evidence Immunogold EM of forebrain synaptosomes; heterologous co-expression and mutagenesis of Kv1.4 clustering

    PMID:8778289 PMID:8938729

    Open questions at the time
    • How PSD-95 itself is targeted to the PSD unknown
    • Whether PSD-95 similarly organizes glutamate receptors not yet tested
  3. 1997 High

    Domain-specific mapping of PDZ interactions—neuroligins via PDZ3, NMDA receptors and K+ channels via PDZ1/2, and SAPAPs via the GK domain—revealed that PSD-95 is a multi-input hub with modular partner specificity.

    Evidence Co-immunoprecipitation from mouse forebrain with PDZ domain binding assays; domain mapping of SAPAP interaction

    PMID:9115257 PMID:9278515

    Open questions at the time
    • Functional consequences of individual domain interactions on synaptic transmission not yet tested
    • Whether PDZ domains act independently or cooperatively unknown
  4. 1999 High

    Multiple discoveries in 1999 expanded PSD-95 from a simple scaffold to a signaling organizer: it scaffolds Fyn to NMDA receptors for tyrosine phosphorylation, bridges metabotropic and ionotropic receptor complexes via Shank/Homer/GKAP, and is linked to microtubules via CRIPT.

    Evidence Co-IP and Fyn-mutant mice for kinase scaffolding; yeast two-hybrid and brain Co-IP for Shank/Homer complex; pulldown and peptide disruption in neurons for CRIPT

    PMID:10433269 PMID:10570482 PMID:9892651

    Open questions at the time
    • How the Shank/Homer/PSD-95 supercomplex assembles stoichiometrically unknown
    • CRIPT-mediated microtubule link not validated in vivo
  5. 2000 High

    Demonstrating that dual palmitoylation at Cys3/5 is essential for vesicular trafficking and postsynaptic targeting of PSD-95 identified the primary membrane-anchoring mechanism and explained why PSD-95 lacks a transmembrane domain yet is membrane-associated.

    Evidence Mutagenesis of Cys3/5, live-cell imaging of vesiculotubular trafficking, subcellular fractionation

    PMID:10629226

    Open questions at the time
    • Identity of the palmitoylating enzyme unknown
    • Whether palmitoylation is reversible and regulatable not yet established
  6. 2003 High

    Gain-of-function electrophysiology showed that PSD-95 overexpression converts silent synapses to active ones by increasing AMPAR content and enhances LTD susceptibility, establishing PSD-95 as a rate-limiting determinant of synaptic AMPAR incorporation.

    Evidence Biolistic transfection in organotypic slices with paired electrophysiology

    PMID:12563010

    Open questions at the time
    • Whether endogenous PSD-95 loss produces the converse phenotype not yet shown
    • Mechanism by which PSD-95 recruits AMPARs (direct vs. indirect) unclear
  7. 2004 High

    Identification of DHHC palmitoyl acyltransferases as the enzymes that palmitoylate PSD-95, and the KO mouse revealing enhanced striatal LTP and altered cocaine responses, together linked PSD-95 palmitoylation to synapse-specific AMPAR regulation and dopamine-glutamate crosstalk in vivo.

    Evidence Screen of 23 DHHC proteins with in vitro palmitoylation assay plus neuronal electrophysiology; PSD-95 KO mouse with behavioral pharmacology and striatal LTP recording

    PMID:14980210 PMID:15603741

    Open questions at the time
    • Which specific DHHC isoform acts at synapses in vivo unknown
    • Mdm2-dependent ubiquitination pathway only partially characterized
  8. 2006 High

    PSD-95 KO mice confirmed the overexpression findings: loss of PSD-95 increases silent synapses on mature spines and shifts NMDAR composition toward NR2B, while in vivo two-photon imaging showed PSD-95 exchanges rapidly between spines with activity-dependent retention kinetics.

    Evidence KO mouse with two-photon glutamate uncaging at single spines; in vivo photoactivation of PAGFP-PSD-95 during sensory deprivation

    PMID:17090216 PMID:17148601

    Open questions at the time
    • What retains PSD-95 at large PSDs molecularly undefined
    • Whether rapid exchange is palmitoylation-dependent not tested
  9. 2007 High

    Structural and trafficking studies revealed the GK domain uses the ancestral GMP-binding pocket for protein-protein interactions (MAP1a), while BDNF/TrkB/PI3K signaling drives Golgi-dependent vesicular delivery of PSD-95 to dendrites, linking growth-factor signaling to scaffold supply.

    Evidence NMR structural model of GK with MAP1a binding; FRAP in neurons with pharmacological and genetic pathway dissection

    PMID:17220895 PMID:17515902

    Open questions at the time
    • Whether PI3K-dependent trafficking requires palmitoylation not addressed
    • MAP1a interaction not validated in vivo at synapses
  10. 2008 High

    Structure-function dissection showed N-terminal dimerization drives basal AMPAR function while SH3-GK domains mediate synaptic localization and LTD; separately, PSD-95 promotes multiinnervated spine formation through PDZ2-nNOS-NO signaling.

    Evidence Mutagenesis with electrophysiology (N-terminal dimerization mutants); EM plus pharmacology and domain deletions for nNOS-dependent synaptogenesis

    PMID:18215622 PMID:19075115

    Open questions at the time
    • How N-terminal dimerization and palmitoylation cooperate structurally unclear
    • Downstream NO targets in synaptogenesis unidentified
  11. 2009 High

    Multiple 2009 studies defined PSD-95 as a regulatory nexus for LTD, dopamine signaling, and serotonin receptor stabilization: DHHC2 was identified as the activity-sensitive synaptic palmitoyltransferase; AKAP150/calcineurin interaction via SH3-GK was shown essential for NMDAR-triggered AMPAR endocytosis; PSD-95 modulates D1 and 5-HT2A/2C receptor trafficking and signaling; and TAP-tag proteomics revealed a 118-protein PSD-95 interactome enriched for schizophrenia genes.

    Evidence DHHC2 live imaging and palmitoylation assay; AKAP150 shRNA and domain mutants with electrophysiology; PSD-95 KO behavioral pharmacology and signaling assays; TAP-tag knockin MS from mouse brain

    PMID:19169250 PMID:19261890 PMID:19455133 PMID:19494135 PMID:19596852

    Open questions at the time
    • How DHHC2 translocation is triggered by activity blockade molecularly unknown
    • Relative contributions of different interactome modules to specific plasticity forms not resolved
  12. 2010 High

    Tyrosine phosphorylation of PSD-95 was mapped to two sites—Tyr523 by Src/Fyn (enhanced in ischemia, required for NMDAR current facilitation) and Tyr533 by c-Abl (required for synaptic clustering)—while the nNOS-PSD-95 interaction was validated as a therapeutic target for excitotoxic injury.

    Evidence In vitro kinase assays with mutagenesis plus neuronal electrophysiology; nNOS-PSD-95 disruption by peptide and small molecule ZL006 in MCAO ischemia model

    PMID:18721130 PMID:20220006 PMID:21102461

    Open questions at the time
    • Whether Tyr523 and Tyr533 phosphorylation are coordinated or independent unknown
    • ZL006 specificity for PSD-95/nNOS not fully characterized
  13. 2011 High

    A convergence of regulatory mechanisms was established: S-nitrosylation competes with palmitoylation at C3/C5; FMRP phosphorylation controls PSD-95 translation via miR-125a/AGO2; Cdk5 gates Mdm2-dependent ubiquitination; Ca²⁺/calmodulin mediates postsynaptic release during homeostatic scaling; and BDNF drives PSD-95 delivery via microtubule spine invasions.

    Evidence Biotin-switch and palmitoylation assays in ZDHHC8 KO; AGO2 Co-IP and FMRP phosphorylation manipulation; Cdk5 genetic/pharmacological inhibition with ubiquitination assay; electrophysiology with CaM-binding mutants; TIRF live imaging of MT dynamics

    PMID:21543610 PMID:21658607 PMID:21745643 PMID:21849563 PMID:22031905

    Open questions at the time
    • Relative dominance of these regulatory inputs during different plasticity paradigms unknown
    • Whether NO and CaM pathways converge at C3/C5 simultaneously not tested
  14. 2012 High

    Developmental onset of PSD-95 expression was shown to be controlled by PTBP1/2-mediated alternative splicing of exon 18, coupling neuronal differentiation programs to synapse maturation through post-transcriptional regulation.

    Evidence PTBP knockdown/re-expression in neurons with RT-PCR splicing and NMD analysis

    PMID:22246437

    Open questions at the time
    • What triggers the developmental downregulation of PTBP2 in specific neuron types not fully defined
    • Whether exon 18 splicing is activity-regulated unknown
  15. 2013 High

    NMR/SAXS structural analysis of the PDZ3-SH3-GK supramodule revealed intramolecular autoinhibition: PDZ3 occludes the SH3 surface, and this is relieved by PDZ3 ligand binding or linker phosphorylation, providing a structural mechanism for allosteric regulation of partner recruitment.

    Evidence NMR, SAXS, and Rosetta computational modeling of MAGUK core

    PMID:23395180

    Open questions at the time
    • Whether this autoinhibition operates in the full-length palmitoylated protein at the PSD unknown
    • Identity of relevant linker kinases not established
  16. 2014 High

    The Ca²⁺/calmodulin–PSD-95 N-terminal interaction was structurally resolved by NMR, explaining how Ca²⁺ influx directly competes with palmitoylation and CDKL5 binding to trigger activity-dependent PSD-95 release from spines.

    Evidence NMR structure of CaM–PSD-95 N-terminus complex, Y12E mutagenesis, live imaging of PSD-95 spine dispersal

    PMID:24705785

    Open questions at the time
    • Whether CaM-mediated release requires prior depalmitoylation or causes it unknown
    • Role of CDKL5 displacement in plasticity not tested
  17. 2016 High

    Two breakthroughs redefined the palmitoylation cycle: ABHD17 thioesterases were identified as the PSD-95-specific depalmitoylating enzymes, and FRET/EM showed palmitoylation switches PSD-95 from compact to extended conformation, with only the extended form binding AMPAR-TARPs and GluN2B-NMDARs.

    Evidence Screen of 38 serine hydrolases with APEGS palmitoylation assay and neuronal knockdown; FRET-based conformation assay with EM and palmitoylation manipulation in PSDs

    PMID:27307232 PMID:27956638

    Open questions at the time
    • How ABHD17 activity is regulated by synaptic activity unknown
    • Whether compact PSD-95 has functions beyond being a palmitoylation-off state unclear
  18. 2017 High

    Crystal structure of PSD-95 GK with phospho-SAPAP peptide revealed phosphorylation-dependent binding, and CaM-PSD-95 charge-inversion experiments established CaM as the effector for homeostatic scaling down, completing the structural and functional logic of PSD-95's major regulatory interfaces.

    Evidence Crystal structure plus biochemical binding and inhibitory peptide assays; NMR with E17R/R126E charge-inversion rescue and mEPSC analysis

    PMID:29118000 PMID:29281827

    Open questions at the time
    • Identity of the SAPAP kinase at synapses not established
    • How CaM-dependent scaling down and LTD mechanisms diverge at PSD-95 unclear
  19. 2018 High

    α-Actinin was identified as a direct anchor for PSD-95 at the postsynaptic membrane via N-terminal K10/K11 residues, providing a palmitoylation-independent retention mechanism; knockdown of α-actinin phenocopied PSD-95 loss.

    Evidence Charge-reversal mutagenesis at K10/K11 and α-actinin E53/E213-D217, shRNA knockdown, electrophysiology

    PMID:29429936

    Open questions at the time
    • How α-actinin and palmitoylation cooperate to set PSD-95 retention quantitatively unclear
    • Whether α-actinin binding is activity-regulated not known
  20. 2021 High

    Pharmacological stabilization of PSD-95 palmitoylation (by inhibiting depalmitoylation) rescued Aβ-induced synaptic weakening by blocking pathological NMDAR C-terminal conformational changes, positioning PSD-95 palmitoylation as a potential intervention point in Alzheimer's disease-related synaptotoxicity.

    Evidence FRET-based NMDAR conformation assay, depalmitoylation inhibition, Co-IP with PP1, electrophysiology

    PMID:34077732

    Open questions at the time
    • Whether sustained depalmitoylation inhibition has adverse effects on normal plasticity unknown
    • In vivo validation in AD mouse models not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how the multiple N-terminal regulatory inputs (palmitoylation, CaM, α-actinin, S-nitrosylation, CDKL5) are hierarchically integrated during specific plasticity events; what regulates ABHD17 depalmitoylase activity; and whether allosteric communication between the PDZ3-SH3 autoinhibitory module and the palmitoylation-dependent conformational switch operates in intact synapses.
  • Stoichiometric assembly rules for PSD-95 nanodomains in living synapses undefined
  • Full-length structural model of palmitoylated PSD-95 in a membrane context not available
  • How PSD-95 interactome composition changes dynamically across different plasticity paradigms remains unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 5 GO:0005198 structural molecule activity 4
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 8 R-HSA-392499 Metabolism of proteins 7 R-HSA-162582 Signal Transduction 5
Partners
ACTN2DLGAP1EFNB3GRIN2AGRIN2BNLGN1SHANK1ZDHHC2
Complex memberships
PSD-95/AKAP150/calcineurin signaling complexPSD-95/SAPAP/Shank/Homer postsynaptic complexPSD-95/nNOS complex

Evidence

Reading pass · 63 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 PSD-95 binds to the cytoplasmic C-termini of neuroligins via its third PDZ domain, while NMDA2 receptors and K+ channels interact with the first and second PDZ domains, demonstrating domain-specific functions for recruiting different proteins to synapses. Co-immunoprecipitation from mouse forebrain, PDZ domain binding assays Science High 9278515
1997 SAPAPs (SAP90/PSD-95-Associated Proteins) specifically interact with PSD-95 through its guanylate kinase domain, are enriched in the postsynaptic density, and induce enrichment of PSD-95 to the plasma membrane. Co-immunoprecipitation, transfection/colocalization in heterologous cells Journal of Biological Chemistry High 9115257
1995 The guanylate kinase domain of PSD-95/SAP90 specifically binds GMP in the micromolar range but exhibits no guanylate kinase enzymatic activity, indicating the GK domain has evolved into a protein-protein interaction module. In vitro nucleotide binding assay (biochemical), enzymatic activity assay FEBS Letters High 7867790
1996 PSD-95 is localized exclusively to the postsynaptic density of forebrain synapses and does not label presynaptic terminals, as demonstrated by immunogold electron microscopy. Immunogold electron microscopy of forebrain synaptosomes Journal of Neuroscience High 8778289
1996 PSD-95 clusters Shaker-type K+ channels (Kv1.4) at the cell surface via PDZ domain interactions with the C-terminal -ETDV motif; mutation of this motif abolishes clustering. Heterologous co-expression, mutagenesis, immunofluorescence clustering assay Neuropharmacology High 8938729
1999 PSD-95 promotes Fyn-mediated tyrosine phosphorylation of NMDA receptor subunit NR2A by scaffolding Fyn to NR2A; different regions of PSD-95 associate with NR2A and Fyn respectively, and PSD-95 also associates with Src, Yes, and Lyn. Co-immunoprecipitation, co-expression in 293T cells, NR2A phosphorylation assay in fyn-mutant mice PNAS High 9892651
1999 Shank proteins bind Homer and PSD-95/GKAP complexes simultaneously, with a single Homer-binding site in Shank; Shank mediates coclustering of mGluR5 with PSD-95/GKAP in the presence of Homer, cross-linking mGluR and NMDA receptor signaling complexes. Co-immunoprecipitation from brain, yeast two-hybrid, colocalization in heterologous cells Neuron High 10433269
1999 CRIPT binds directly to the third PDZ domain (PDZ3) of PSD-95 and also binds microtubules, linking PSD-95 to the microtubule cytoskeleton; disrupting CRIPT-PSD-95 interaction inhibits synaptic clustering of PSD-95 but not NMDA receptors. Pulldown, co-immunoprecipitation, peptide disruption in hippocampal neurons, immunofluorescence Nature Neuroscience High 10570482
1999 Cypin, identified by affinity chromatography as a major PSD-95-binding protein in brain, perturbs postsynaptic trafficking of PSD-95 and SAP-102 when overexpressed in hippocampal neurons. Affinity chromatography, overexpression in hippocampal neurons, immunofluorescence Neuron Medium 10595517
2000 Dual palmitoylation at the N-terminus of PSD-95 (at cysteines 3 and 5) is required for its trafficking through vesiculotubular structures in a microtubule-dependent manner and is essential for postsynaptic targeting and ion channel clustering; mutations blocking dual palmitoylation abolish both functions. Mutagenesis, live-cell imaging, subcellular fractionation, trafficking assays Journal of Cell Biology High 10629226
2000 PSD-95 suppresses the activity of Kir2.3 inwardly rectifying K+ channels by >50% through a molecular association involving internal interaction sites beyond the C-terminal PDZ motif. Yeast two-hybrid, co-immunoprecipitation, electrophysiology in HEK-293 cells Journal of Neuroscience Medium 10627592
2000 PSD-95 is a substrate for calpain; calpain cleaves PSD-95 into 50 and 36 kDa fragments following calcium activation or NMDA treatment, and this truncation contributes to PSD-95 turnover. In vitro calpain cleavage assay, calcium treatment of brain sections, NMDA treatment of hippocampal cultures, Western blotting Neuroscience Letters High 10825658
2001 DLG4/PSD-95 interacts with the complement receptor CD46 specifically through its Cyt1 cytoplasmic domain, and this interaction is required for polarized expression of CD46 in epithelial cells. Yeast two-hybrid, co-immunoprecipitation, dominant-negative expression in epithelial cells Journal of Biological Chemistry Medium 11714708
2001 Erbin, a PDZ domain-containing protein concentrated at postsynaptic membranes, directly interacts with PSD-95 in transfected cells and synaptosomes, linking ErbB2 to the PSD-95 scaffold. Co-immunoprecipitation from synaptosomes and transfected cells Journal of Biological Chemistry Medium 11279080
2001 NMR structure of the PDZ1 domain of PSD-95/SAP90 reveals structural differences from PDZ2 and PDZ3 that underlie unique binding specificities; PDZ1 binds GluR6, Kv1.4, and CRIPT C-terminal peptides with affinities from 1.5 to 160 µM. NMR structural determination, fluorescence anisotropy binding assay Journal of Biological Chemistry High 11744724
2002 Densin-180 links to PSD-95 indirectly through MAGUIN-1: Densin-180 PDZ domain binds MAGUIN-1 C-terminal motif, and MAGUIN-1 binds the first PDZ domain of PSD-95, forming a ternary complex at postsynaptic spines. Yeast two-hybrid, co-immunoprecipitation from rat brain, co-transfection/colocalization Genes to Cells Medium 12390249
2003 Overexpression of PSD-95 in cortical pyramidal neurons increases AMPA receptor-mediated synaptic transmission by increasing the number of synapses expressing AMPARs (converting silent to active synapses) and greatly enhances the probability of LTD. Biolistic transfection in organotypic slices, electrophysiology, paired-pulse ratio analysis Journal of Physiology High 12563010
2003 PSD-95 palmitoylation recruits Kv1.4 (but not Kv4.2) channels into lipid rafts via PDZ domain interaction; palmitoylation-deficient PSD-95 fails to recruit Kv1.4 to lipid rafts. Lipid raft fractionation, co-expression in heterologous cells, mutagenesis Journal of Biological Chemistry Medium 14559911
2004 DHHC palmitoyl acyltransferases (P-PATs) specifically palmitoylate PSD-95 in vitro and in vivo; inhibition of P-PAT activity in neurons reduces palmitoylation and synaptic clustering of PSD-95 and diminishes AMPA receptor-mediated neurotransmission. In vitro palmitoylation assay with 23 mammalian DHHC proteins, neuronal loss-of-function, electrophysiology Neuron High 15603741
2004 PSD-95 KO mice show increased striatal LTP at frontocortico-accumbal synapses, augmented acute locomotor response to cocaine, but no additional behavioral plasticity to chronic cocaine, identifying PSD-95 as a regulator of dopamine-mediated synaptic plasticity. Targeted gene deletion, electrophysiology (LTP), behavioral pharmacology Neuron High 14980210
2004 Neuregulin-1 intracellular domain (Nrg-ICD) enhances transcription of the PSD-95 promoter by binding to the zinc-finger transcription factor Eos in the nucleus, providing an activity-dependent mechanism for PSD-95 upregulation. Reporter assay, co-immunoprecipitation, in vivo expression analysis in mouse cochlea Nature Neuroscience Medium 15494726
2004 IRSp53 links postsynaptic Shank1 to PSD-95 via its C-terminal PDZ binding motif interacting with PDZ2 of PSD-95, forming a triple complex (Shank1/IRSp53/PSD-95) at postsynaptic sites. Co-immunoprecipitation from brain, pull-down, immunocytochemistry in neurons Journal of Neurochemistry Medium 15255944
2004 PSD-95 ubiquitination by Mdm2 is proteasome-dependent and negatively correlated with GluR1 internalization; overexpression of PSD-95 inhibits neurotransmitter-stimulated GluR1 endocytosis. Immunofluorescence quantification in neurons, overexpression, ubiquitination assay Neuropharmacology Medium 15458847
2006 PSD-95 KO mice show reduced AMPA receptor-mediated synaptic transmission, increased proportion of silent synapses on morphologically mature spines, and greater NR2B contribution to NMDAR currents, demonstrating a synapse-specific role for PSD-95 in AMPAR incorporation. KO mouse, two-photon glutamate uncaging, electrophysiology PNAS High 17148601
2006 DLG4/PSD-95 protein is degraded by HPV18 E6 in an E6AP-dependent manner; E6 binds DLG4 via its C-terminal PDZ-binding motif, and forced expression of DLG4 inhibits tumorigenicity of cervical cancer cells. In vitro degradation assay, shRNA knockdown of E6AP, Western blotting, tumorigenicity assay Journal of Virology Medium 17121805
2006 In vivo two-photon imaging shows synaptic PSD-95 turns over rapidly (retention time ~22–63 min at P10–P21) by diffusion exchange between spines; large PSDs capture and retain more PSD-95, and sensory deprivation decreases retention times. Two-photon microscopy with photoactivatable GFP (FRAP/photoactivation) in vivo PLoS Biology High 17090216
2007 The guanylate kinase domain of PSD-95 binds microtubule-associated protein MAP1a through the canonical GMP-binding region; structural modeling reveals GK has adopted conformational flexibility of the ancestral enzyme to bind diverse protein partners. NMR structural model, in vitro binding assay, consensus sequence determination Nature Structural & Molecular Biology High 17220895
2007 BDNF activates TrkB→PI3K→Akt signaling to transport PSD-95 to dendrites via Golgi-dependent vesicular transport; NMDAR stimulation mimics this trafficking in a BDNF- and PI3K-dependent manner. FRAP in cultured neurons, pharmacological inhibition, TrkB dominant-negative, Golgi disruption Nature Neuroscience High 17515902
2007 PSD-95 interacts with the D1 dopamine receptor via the D1 C-terminal tail and PSD-95 N-terminus (not PDZ domains); this interaction inhibits D1-mediated cAMP signaling by enhancing constitutive dynamin-dependent D1 endocytosis. Co-immunoprecipitation, cAMP assay, surface biotinylation, dynamin dominant-negative, PSD-95 KO mice behavioral pharmacology Journal of Biological Chemistry High 17369255
2008 The N-terminal domain dimerization of PSD-95 is important for its effect on basal synaptic AMPAR function, while SH3-GK domains are required for PSD-95 synaptic localization; point mutants Q15A and E17R maintain AMPAR effects but block LTD by producing a C-terminal dominant-negative fragment. Mutagenesis, viral overexpression in neurons, electrophysiology, proteolysis assay Neuron High 18215622
2008 PSD-95 overexpression promotes synaptogenesis and multiinnervated spine formation through its PDZ2 domain interaction with nNOS and subsequent NO signaling; deletion of PDZ2 or pharmacological blockade of NOS prevents multisynapse formation. Electron microscopy, siRNA, pharmacology, PDZ domain deletion mutants in hippocampal slices Journal of Cell Biology High 19075115
2009 DHHC2, a dendritically localized palmitoyl acyltransferase, mediates activity-sensitive palmitoylation of PSD-95 and translocates to the postsynaptic density upon activity blockade, driving synaptic clustering of PSD-95 and AMPA receptors. Palmitoylation assay, live imaging, DHHC2 knockdown/overexpression in neurons Journal of Cell Biology High 19596852
2009 PSD-95 interaction with AKAP150 (via SH3-GK domains) is required for NMDAR-triggered endocytosis of synaptic AMPARs and LTD; AKAP150 positions calcineurin in the appropriate subsynaptic domain for this process. shRNA knockdown, domain deletion mutants, point mutation L460P, AKAP150 mutant, electrophysiology Nature Neuroscience High 19169250
2009 PSD-95 forms a ternary complex with D1 dopamine receptor and NR1 NMDA receptor subunit; PSD-95 inhibits D1-NR1 association and uncouples NMDA receptor-dependent enhancement of D1 signaling partly by disinhibiting D1 internalization. Co-immunoprecipitation, cAMP assay, PSD-95 knockdown in neurons, electrophysiology Journal of Neuroscience High 19261890
2009 Tandem affinity purification of PSD-95 from mouse brain recovers 118 proteins including glutamate receptors, K+ channels, scaffolding and signaling proteins organized into network clusters; schizophrenia-associated genes significantly correlate with glutamate receptor clusters. TAP-tag knockin mouse, native co-purification, mass spectrometry, network analysis Molecular Systems Biology High 19455133
2009 Within individual dendritic spines, PSD-95 is highly stable (more so than CaMKII or GluR2/Stargazin); N-terminal palmitoylation and PDZ1/2 domain interactions stabilize PSD-95 in the PSD, SH3 domain is required for forming a stable lattice, and NMDA receptor activation via chemical LTD rapidly destabilizes PSD-95 via PDZ1/2. Two-photon photoactivation of PAGFP-tagged PSD-95 mutants in CA1 neurons, domain mutagenesis Journal of Neuroscience High 19828799
2009 PSD-95 is essential for normal 5-HT2A and 5-HT2C serotonin receptor expression and function in vivo; PSD-95 maintains receptor expression by promoting apical dendritic targeting and stabilizing receptor turnover, and mediates downstream signaling from these GPCRs. PSD-95 null mice, immunohistochemistry, signaling assays, behavioral pharmacology Journal of Neuroscience High 19494135
2010 PSD-95 clusters Pyk2 at postsynaptic sites and induces Pyk2 trans-autophosphorylation at Tyr402 (activation); Ca2+/calmodulin-stimulated binding of Pyk2 to PSD-95 mediates this clustering and is required for LTP in hippocampal CA1. Co-immunoprecipitation, in vitro autophosphorylation assay, antibody-induced oligomerization, electrophysiology Journal of Neuroscience High 20071509
2010 Cerebral ischemia induces interaction of nNOS with PSD-95; disrupting this interaction (via nNOS-N1-133 overexpression or ZL006 compound) prevents glutamate excitotoxicity and cerebral ischemic damage in mice and rats. Co-immunoprecipitation, viral overexpression, pharmacological inhibition, MCAO model, behavioral assays Nature Medicine High 21102461
2010 c-Abl kinase phosphorylates PSD-95 at tyrosine 533; c-Abl associates with PSD-95 at postsynaptic sites, and inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation and synaptic clustering of PSD-95. Co-immunoprecipitation, in vitro kinase assay, mutagenesis (Y533F), c-Abl inhibitor/genetic knockdown, immunofluorescence Journal of Neuroscience High 20220006
2010 Muscarinic receptor-induced LTD of NMDAR EPSCs involves hippocalcin binding to the SH3 region of PSD-95 under basal conditions; Ca2+ causes hippocalcin to translocate to the plasma membrane, dissociating PSD-95 from NMDARs and allowing AP2 to bind and initiate dynamin-dependent NMDAR endocytosis. Co-immunoprecipitation, pharmacology, dominant-negative constructs, electrophysiology Nature Neuroscience High 20852624
2011 miR-125a targeting PSD-95 mRNA allows reversible translational inhibition; FMRP phosphorylation promotes an AGO2-miR-125a inhibitory complex on PSD-95 mRNA, while mGluR signaling leads to FMRP dephosphorylation and release of AGO2, enabling PSD-95 translation. Biochemical fractionation, Co-IP of AGO2 complexes, miR-125a inhibition, FMRP phosphorylation assays, dendritic spine morphology analysis Molecular Cell High 21658607
2011 S-nitrosylation of PSD-95 at cysteines 3 and 5 (the palmitoylation sites) competes with palmitoylation; NO production inhibits PSD-95 palmitoylation in cerebellar granule cells, decreasing PSD-95 synaptic clusters; loss of palmitoylation increases PSD-95 nitrosylation. Biotin-switch assay, palmitoylation assay, immunofluorescence, ZDHHC8 KO mice Neuron High 21745643
2011 PSD-95 PDZ1/2 domains are required for synaptic scaling down, while either PSD-95 or PSD-93 can support scaling up; synaptic PSD-95 abundance is bidirectionally regulated by activity but changes in PSD-95 abundance alone are not sufficient to drive homeostatic scaling. shRNA knockdown, overexpression, dominant-negative domain mutants, electrophysiology in hippocampal neurons Journal of Neuroscience High 21543610
2011 Cdk5 activity suppresses Mdm2-dependent ubiquitination of PSD-95; reduction of Cdk5 activity increases Mdm2-PSD-95 interaction and PSD-95 ubiquitination, which promotes interaction of PSD-95 with β-adaptin/AP-2, suggesting a mechanism for NMDA-triggered AMPAR endocytosis. Genetic and pharmacological Cdk5 inhibition in mice, co-immunoprecipitation, ubiquitination assay Journal of Neuroscience Medium 21849563
2011 BDNF-induced increase in PSD-95 in dendritic spines requires dynamic microtubule invasions into spines; peaks of MT polymerization into spines correspond to rapid PSD-95 increases in the spine head, and pharmacological inhibition of MT dynamics abolishes BDNF-induced PSD-95 increase. TIRF microscopy, live imaging, pharmacological MT inhibition in hippocampal neurons Journal of Neuroscience High 22031905
2011 BDNF/TrkB signaling regulates PSD-95 palmitoylation and synaptic transport through PLCγ and PKMζ; PKMζ selectively phosphorylates the palmitoylation enzyme ZDHHC8, and PKMζ inhibition reduces synaptic PSD-95 accumulation rescued by ZDHHC8 overexpression. In vivo pharmacology, viral rescue with ZDHHC8, immunofluorescence in visual cortex Journal of Neuroscience High 21849550
2012 PTBP1 and PTBP2 repress PSD-95 (Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay; sequential loss of PTBP1 then PTBP2 during development allows exon 18 inclusion and PSD-95 expression, which is required for glutamatergic synapse maturation. RT-PCR splicing assays, PTBP knockdown/re-expression in neurons, NMD analysis, synapse morphology Nature Neuroscience High 22246437
2013 NMR, SAXS, and computational modeling reveal that the MAGUK core (PDZ3-SH3-GK) of PSD-95 exists in a dynamic structural ensemble where PDZ3 interacts directly with SH3 via its peptide binding groove; this interaction is weakened by PDZ3 ligands and linker phosphorylation. NMR, small-angle X-ray scattering, Rosetta modeling Structure High 23395180
2014 Ca2+/calmodulin binds the N-terminus of PSD-95 (residues 1–16) as revealed by NMR structure; CaM blocks palmitoylation of C3 and C5 and binding of CDKL5, causing Ca2+-induced release of PSD-95 from postsynaptic membranes; PSD-95 Y12E mutant impairs CaM binding and Ca2+-induced release. NMR structure, palmitoylation assay, mutagenesis (Y12E), live imaging of PSD-95 release in spines EMBO Journal High 24705785
2014 Ephrin-B3 directly interacts with PSD-95 and controls its synaptic localization and stability; activity-induced MAPK phosphorylation of ephrin-B3 at Ser332 disperses it from synapses, preventing PSD-95 interaction and increasing PSD-95 turnover. Super-resolution imaging, co-immunoprecipitation, mutagenesis, FRAP, in vivo models Nature Neuroscience High 26479588
2015 LGI1-ADAM22 complex regulates PSD-95 function in synapse maturation; in the absence of LGI1, PSD-95 (but not SAP102) cannot modulate synaptic transmission, and ADAM22 maintains excitatory synapses through PDZ domain interactions. Electrophysiology, viral rescue experiments, co-immunoprecipitation, LGI1 and ADAM22 KO analysis PNAS High 26178195
2016 ABHD17A, 17B, and 17C serine hydrolases are specific PSD-95 depalmitoylating enzymes; located in recycling endosomes and synaptic fraction; ABHD17 expression reduces PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors; most PSD-95 undergoes rapid palmitoylation cycling. Serine hydrolase activity screen (38 proteins), APEGS assay, ABHD17 knockdown in neurons, immunofluorescence Journal of Neuroscience High 27307232
2016 Palmitoylation changes PSD-95 conformation from compact to extended; only palmitoylated (extended) PSD-95 associates with AMPARs (via TARPs) or NMDARs (via GluN2B); within PSDs PSD-95 is oriented perpendicular to membrane with palmitoylated N-terminus at the membrane; changing PSD-95 palmitoylation alters AMPAR but not NMDAR levels. FRET, electron microscopy, mutagenesis, subcellular fractionation, palmitoylation manipulation in PSDs PNAS High 27956638
2017 TAOK2 directly phosphorylates Septin7, which translocates to the spine and associates with and stabilizes PSD-95, promoting dendritic spine maturation; TAOK2 depletion causes mislocalized shaft-synapses and loss of NMDA receptor-mediated calcium compartmentalization. Chemical genetics, mass spectrometry, in vitro kinase assay, co-immunoprecipitation, knockdown in neurons Neuron High 28065648
2017 PSD-95/SAPAP interaction requires phosphorylation of N-terminal repeat sequences of SAPAPs; crystal structure of PSD-95 GK domain with phospho-SAPAP peptide reveals molecular basis of phosphorylation-dependent interaction; non-phosphorylated GK inhibitory peptides block PSD-95/SAPAP interaction and synaptic maturation. Crystal structure determination, biochemical binding assays, neuronal overexpression/inhibitory peptides, electrophysiology Cell Reports High 29281827
2017 Ca2+/calmodulin binding to the N-terminus of PSD-95 (at E17 interacting with CaM R126) mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic synaptic scaling down; E17R mutation prevents scaling down, rescued by CaM R126E charge inversion. NMR structural analysis, mutagenesis with charge-inversion rescue, electrophysiology (mEPSC analysis) EMBO Journal High 29118000
2018 α-Actinin binds directly to the N-terminus of PSD-95 (at K10/K11); knockdown of α-actinin phenocopies PSD-95 knockdown; charge-reversal mutations at PSD-95 K10/K11 or α-actinin E53/E213-D217 impair PSD-95 postsynaptic localization and AMPAR anchoring in parallel. Co-immunoprecipitation, mutagenesis (charge-reversal), shRNA knockdown, immunofluorescence, electrophysiology Neuron High 29429936
2019 PKA phosphorylates NLGN1 at S839 near its PDZ ligand, reducing PSD-95 binding; a phosphomimetic S839D mutation reduces PSD-95 interaction and synaptic NLGN1 expression; disruption of NLGN1-PSD-95 interaction decreases surface NLGN1 and NLGN1-mediated synaptic enhancement. Co-immunoprecipitation, surface biotinylation, mutagenesis, in vitro phosphorylation, electrophysiology PNAS High 31138690
2021 Increased PSD-95 blocks Aβ-induced modification of the NMDAR C-terminal domain conformation and its interaction with PP1; pharmacological inhibition of PSD-95 depalmitoylation increases synaptic PSD-95 and rescues Aβ-induced synaptic weakening. FRET-based conformation assay, co-immunoprecipitation, pharmacological depalmitoylation inhibition, electrophysiology Cell Reports High 34077732
2009 DGKζ is targeted to excitatory synapses through direct PDZ interaction with PSD-95; overexpression increases dendritic spine number in a catalytic-activity and PSD-95 binding-dependent manner; DGKζ KO mice show reduced spine density and excitatory synaptic transmission. Co-immunoprecipitation, overexpression/KO in neurons and mice, time-lapse imaging, electrophysiology EMBO Journal High 19229292
2008 GLT1b glutamate transporter interacts with PSD-95 PDZ domains via its C-terminal PDZ-binding motif; co-expression of GLT1b with PSD-95 increases transporter Vmax by decreasing GLT1b endocytosis rate. Co-immunoprecipitation from rat brain, heterologous co-expression, transport assay, surface expression measurement Journal of Neurochemistry Medium 18248606
2009 Brain ischemia increases tyrosine phosphorylation of PSD-95 at Tyr523 by Src family kinases; Y523F mutation reduces Src/Fyn-mediated phosphorylation and abolishes PSD-95-facilitated NMDA receptor currents in hippocampal neurons. In vitro kinase assay with purified Src/Fyn, mutagenesis, co-expression in COS7 cells, hippocampal neuron electrophysiology, rat ischemia model Biochemical Journal High 18721130

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 877 10433269
1997 Binding of neuroligins to PSD-95. Science (New York, N.Y.) 607 9278515
2004 Identification of PSD-95 palmitoylating enzymes. Neuron 451 15603741
2012 Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 359 22388811
2010 Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nature medicine 359 21102461
2005 Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiology of disease 340 16242627
1999 PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Proceedings of the National Academy of Sciences of the United States of America 333 9892651
1997 SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. The Journal of biological chemistry 314 9115257
2006 Synapse-specific regulation of AMPA receptor function by PSD-95. Proceedings of the National Academy of Sciences of the United States of America 313 17148601
2004 Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 312 14980210
2011 Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. Molecular cell 310 21658607
2006 Rapid redistribution of synaptic PSD-95 in the neocortex in vivo. PLoS biology 279 17090216
2007 BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation. Nature neuroscience 266 17515902
1996 PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 258 8778289
2003 PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex. The Journal of physiology 253 12563010
2000 Dual palmitoylation of PSD-95 mediates its vesiculotubular sorting, postsynaptic targeting, and ion channel clustering. The Journal of cell biology 229 10629226
2009 Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Molecular systems biology 211 19455133
1998 Immunocytochemical localization of the postsynaptic density protein PSD-95 in the mammalian retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 202 9822767
2012 PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nature neuroscience 201 22246437
2016 Identification of PSD-95 Depalmitoylating Enzymes. The Journal of neuroscience : the official journal of the Society for Neuroscience 189 27307232
2009 Mobile DHHC palmitoylating enzyme mediates activity-sensitive synaptic targeting of PSD-95. The Journal of cell biology 186 19596852
2011 Regulation of AMPA receptor surface diffusion by PSD-95 slots. Current opinion in neurobiology 175 22051694
2014 The relationship between PSD-95 clustering and spine stability in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience 170 24501349
2008 Molecular dissociation of the role of PSD-95 in regulating synaptic strength and LTD. Neuron 163 18215622
2009 A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nature neuroscience 158 19169250
2007 Composition of the synaptic PSD-95 complex. Molecular & cellular proteomics : MCP 145 17623647
2008 PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling. The Journal of cell biology 141 19075115
2004 Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nature neuroscience 135 15494726
2011 S-nitrosylation and S-palmitoylation reciprocally regulate synaptic targeting of PSD-95. Neuron 133 21745643
1996 Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology 129 8938729
2011 BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions. The Journal of neuroscience : the official journal of the Society for Neuroscience 121 22031905
2021 PSD-95 protects synapses from β-amyloid. Cell reports 114 34077732
2008 Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. The international journal of neuropsychopharmacology 113 18570704
2017 TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation. Neuron 112 28065648
2011 PSD-95 and PSD-93 play critical but distinct roles in synaptic scaling up and down. The Journal of neuroscience : the official journal of the Society for Neuroscience 110 21543610
2009 Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 19828799
2009 PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 101 19494135
2000 Neuronal inwardly rectifying K(+) channels differentially couple to PDZ proteins of the PSD-95/SAP90 family. The Journal of neuroscience : the official journal of the Society for Neuroscience 100 10627592
2019 PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment. Scientific reports 99 31263190
1999 Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95. Nature neuroscience 93 10570482
2010 Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95. Nature neuroscience 92 20852624
2003 Differential recruitment of Kv1.4 and Kv4.2 to lipid rafts by PSD-95. The Journal of biological chemistry 90 14559911
1999 Cypin: a cytosolic regulator of PSD-95 postsynaptic targeting. Neuron 86 10595517
2001 Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95. The Journal of biological chemistry 84 11279080
2015 The LGI1-ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function. Proceedings of the National Academy of Sciences of the United States of America 82 26178195
2011 Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain. Molecular therapy : the journal of the American Society of Gene Therapy 78 21427709
2017 Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants. Nature communications 76 28874660
2016 Palmitoylation regulates glutamate receptor distributions in postsynaptic densities through control of PSD95 conformation and orientation. Proceedings of the National Academy of Sciences of the United States of America 75 27956638
2015 Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 73 25948262
2014 Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 25274829
2004 A proteasome-sensitive connection between PSD-95 and GluR1 endocytosis. Neuropharmacology 72 15458847
1998 BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein. The Journal of biological chemistry 72 9756850
2022 Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners. International journal of molecular sciences 71 35457207
2007 Inhibition of the dopamine D1 receptor signaling by PSD-95. The Journal of biological chemistry 70 17369255
2022 Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer's disease. Alzheimer's research & therapy 69 35461266
2016 Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. Molecular neurobiology 69 26884267
2011 Loss of PSD-95 enrichment is not a prerequisite for spine retraction. The Journal of neuroscience : the official journal of the Society for Neuroscience 69 21865455
2004 Synaptic targeting of neuroligin is independent of neurexin and SAP90/PSD95 binding. Molecular and cellular neurosciences 68 15519238
2014 Postsynaptic localization of PSD-95 is regulated by all three pathways downstream of TrkB signaling. Frontiers in synaptic neuroscience 67 24744726
2009 PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex. The Journal of neuroscience : the official journal of the Society for Neuroscience 67 19261890
2000 Calpain-mediated degradation of PSD-95 in developing and adult rat brain. Neuroscience letters 67 10825658
1995 Nucleotide binding by the synapse associated protein SAP90. FEBS letters 67 7867790
2004 Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95. Journal of neurochemistry 66 15255944
2014 Durable fear memories require PSD-95. Molecular psychiatry 64 25510511
2010 Postsynaptic clustering and activation of Pyk2 by PSD-95. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 20071509
2001 Knockdown of PSD-95/SAP90 delays the development of neuropathic pain in rats. Neuroreport 64 11711866
2000 Expression of PSD-95/SAP90 is critical for N-methyl-D-aspartate receptor-mediated thermal hyperalgesia in the spinal cord. Neuroscience 64 10854750
2015 Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis. Cell death and differentiation 63 25678324
2011 TrkB and protein kinase Mζ regulate synaptic localization of PSD-95 in developing cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 21849550
2014 Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 25505322
2018 α-Actinin Anchors PSD-95 at Postsynaptic Sites. Neuron 61 29429936
2014 Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release. The EMBO journal 60 24705785
2006 E6AP-dependent degradation of DLG4/PSD95 by high-risk human papillomavirus type 18 E6 protein. Journal of virology 60 17121805
2002 Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1. Genes to cells : devoted to molecular & cellular mechanisms 59 12390249
2015 Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3. Nature neuroscience 58 26479588
1999 Distinct structural requirements for clustering and immobilization of K+ channels by PSD-95. The Journal of general physiology 58 9874689
2017 Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs. Cell reports 57 29281827
2009 Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. The EMBO journal 57 19229292
2013 Supertertiary structure of the MAGUK core from PSD-95. Structure (London, England : 1993) 55 23395180
2001 A functional interaction between CD46 and DLG4: a role for DLG4 in epithelial polarization. The Journal of biological chemistry 55 11714708
2011 Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 21849563
2000 Sema4c, a transmembrane semaphorin, interacts with a post-synaptic density protein, PSD-95. The Journal of biological chemistry 54 11134026
2019 PSD-95 binding dynamically regulates NLGN1 trafficking and function. Proceedings of the National Academy of Sciences of the United States of America 52 31138690
2010 Synaptic clustering of PSD-95 is regulated by c-Abl through tyrosine phosphorylation. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 20220006
2014 Motor impairments, striatal degeneration, and altered dopamine-glutamate interplay in mice lacking PSD-95. Journal of neurogenetics 50 24702501
2021 Plasmin-resistant PSD-95 inhibitors resolve effect-modifying drug-drug interactions between alteplase and nerinetide in acute stroke. Science translational medicine 49 33827973
2014 G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility. RNA (New York, N.Y.) 49 25406362
2013 A broadly applicable high-throughput screening strategy identifies new regulators of Dlg4 (Psd-95) alternative splicing. Genome research 45 23636947
2005 Interaction between SAP97 and PSD-95, two Maguk proteins involved in synaptic trafficking of AMPA receptors. The Journal of biological chemistry 42 16332687
2007 The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved motif in MAP1a. Nature structural & molecular biology 40 17220895
2001 The PDZ1 domain of SAP90. Characterization of structure and binding. The Journal of biological chemistry 40 11744724
2009 Increased tyrosine phosphorylation of PSD-95 by Src family kinases after brain ischaemia. The Biochemical journal 39 18721130
2014 Epigenetic upregulation of PSD-95 contributes to the rewarding behavior by morphine conditioning. European journal of pharmacology 38 24704371
2010 A cyclic peptide targeted against PSD-95 blocks central sensitization and attenuates thermal hyperalgesia. Neuroscience 37 20167266
2006 Structural modeling of protein interactions by analogy: application to PSD-95. PLoS computational biology 36 17096593
2017 Ca2+/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down. The EMBO journal 35 29118000
2015 Neuroprotective Effects of a PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury. Molecular neurobiology 35 26520452
2004 Localization of synapsin-I and PSD-95 in developing postnatal rat cerebellar cortex. Brain research. Developmental brain research 35 15246689
2013 Bidirectional control of postsynaptic density-95 (PSD-95) clustering by Huntingtin. The Journal of biological chemistry 34 24347167
2008 The glutamate transporter GLT1b interacts with the scaffold protein PSD-95. Journal of neurochemistry 33 18248606