Affinage

PSD

PH and SEC7 domain-containing protein 1 · UniProt A5PKW4

Length
1024 aa
Mass
109.5 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 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

PSD (EFA6A) is a plasma membrane-associated guanine nucleotide exchange factor that, through its Sec7 domain, catalyzes GDP/GTP exchange exclusively on the small GTPase ARF6 and not ARF1, with selectivity dictated by the Sec7 and ARF core domains independent of the myristoylated N-terminal helix (PMID:10075920, PMID:11342560). Its PH domain targets it to PI(4,5)P2-rich plasma membrane invaginations and ruffles while a conserved coiled-coil-containing C-terminal region drives actin-based membrane protrusions (PMID:10075920, PMID:12082148). Through ARF6 activation it governs endosomal membrane recycling and clathrin-mediated endocytosis—activity stimulated by direct binding to the endophilin N-BAR domain, which it recruits to membrane ruffles to control transferrin internalization (PMID:10075920, PMID:24979773). PSD couples this GEF activity and its actin-remodeling C-terminus to epithelial tight junction biogenesis, stabilizing the apical actin ring and retaining occludin upon E-cadherin engagement, a function gated by USP9x-mediated deubiquitination that transiently stabilizes PSD at nascent junctions (PMID:14668475, PMID:20339350). In neurons, PSD promotes ARF6-dependent filopodium-to-spine conversion and dendritic spine maturation (PMID:16672654), and at the axon initial segment it restricts Rab11/integrin vesicle entry into axons to limit regeneration (PMID:28935671). Beyond its GEF function, the EFA6/Drosophila Efa6 N-terminal microtubule elimination domain (MTED) directly binds tubulin and inhibits cortical microtubule polymerization, independent of ARF GEF activity, to regulate axon growth and branching (PMID:31718774). PSD also acts upstream of ARF6/ERK signaling to drive glioma invasion (PMID:16452216) and is positioned at the leading edge of migrating cells via CD13 within an IQGAP1/ARF6 complex that promotes β1 integrin recycling (PMID:31040262).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Established PSD/EFA6A as an ARF6-specific GEF and linked it to membrane recycling and actin remodeling, defining its core molecular activity.

    Evidence In vitro GEF nucleotide exchange assays, immunofluorescence localization, dominant-negative ARF6/Rac1, transferrin recycling assay

    PMID:10075920

    Open questions at the time
    • Did not resolve structural basis of ARF6 selectivity
    • Upstream membrane recruitment cues undefined
  2. 2001 High

    Mapped the determinants of ARF6 versus ARF1 selectivity to the Sec7 and ARF core domains, showing the myristoylated helix is dispensable.

    Evidence Reconstituted in vitro GEF assay on phospholipid membranes with isolated Sec7 and ARF core domains, specificity mapping

    PMID:11342560

    Open questions at the time
    • Atomic-resolution contacts not defined
    • In-cell relevance of selectivity not tested
  3. 2002 Medium

    Identified the PH domain (PI(4,5)P2 binding) and a conserved C-terminal coiled-coil as separable membrane-targeting and protrusion-promoting modules distinct from catalysis.

    Evidence Domain deletion/swap overexpression in BHK cells, coiled-coil mutagenesis, immunofluorescence

    PMID:12082148

    Open questions at the time
    • Direct lipid-binding affinity not quantified
    • Coiled-coil partner not identified
  4. 2003 Medium

    Connected PSD to epithelial tight junction formation, showing both Sec7 catalysis and the actin-remodeling C-terminus are required to stabilize the apical actin ring and retain occludin.

    Evidence Calcium switch assay, Triton X-100 fractionation, catalytic-dead and C-terminal deletion constructs, immunofluorescence in MDCK cells

    PMID:14668475

    Open questions at the time
    • Direct effectors linking actin ring to occludin retention unresolved
    • Single cell-type evidence
  5. 2004 High

    Demonstrated ARF6-dependent partner interactions (TWIK1 channel) and a neuronal role in dendritic spine formation, broadening PSD function from epithelia to neurons.

    Evidence Co-IP, yeast two-hybrid, siRNA knockdown, dominant-negative ARF6, live spine imaging, in situ hybridization, catalytic-dead overexpression in hippocampal neurons

    PMID:15009133 PMID:15540117 PMID:16672654

    Open questions at the time
    • Opposing dendritic effects of catalytic-dead mutant versus spine phenotype not reconciled
    • TWIK1 interaction lacks reciprocal validation
  6. 2006 Medium

    Extended PSD/ARF6 signaling to disease (glioma invasion via ERK) and confirmed family-wide postsynaptic enrichment of EFA6 ARF6-GEFs.

    Evidence Matrigel invasion assays, catalytic-dead and dominant-negative epistasis, MEK inhibitor, ARF pull-down GEF assay, subcellular fractionation

    PMID:16452216 PMID:16707115

    Open questions at the time
    • In vivo tumor relevance not established
    • Mechanism coupling ARF6 to ERK undefined
  7. 2007 Medium

    Identified alpha-actinin-1 as a C-terminal interactor at dendritic spines, providing a candidate link between PSD and the spine actin cytoskeleton.

    Evidence Yeast two-hybrid, immunofluorescence co-localization, subcellular fractionation in hippocampal neurons

    PMID:17298598

    Open questions at the time
    • Direct binding not confirmed by in vitro pulldown
    • Functional consequence of interaction untested
  8. 2010 High

    Revealed PSD is regulated post-translationally by USP9x deubiquitination, stabilizing it transiently at nascent junctions to enable tight junction biogenesis.

    Evidence Reciprocal siRNA knockdown, co-IP, overexpression rescue, immunofluorescence at primordial junctions

    PMID:20339350

    Open questions at the time
    • E3 ligase that ubiquitinates PSD unidentified
    • Ubiquitination site(s) not mapped
  9. 2014 High

    Defined endophilin as a direct activator of PSD GEF activity, integrating ARF6 activation with clathrin-mediated endocytosis.

    Evidence Yeast two-hybrid, in vitro pulldown with purified proteins, GEF stimulation assay, lipid competition, transferrin internalization rescue

    PMID:24979773

    Open questions at the time
    • Structural basis of Sec7/N-BAR competition unresolved
    • Physiological setting of endophilin stimulation in vivo not shown
  10. 2017 High

    Localized PSD to the axon initial segment as an intrinsic gatekeeper of selective axon transport, restricting Rab11/integrin entry to limit axon regeneration.

    Evidence shRNA/siRNA knockdown, laser axotomy, live imaging of Rab11/integrin transport, overexpression, immunofluorescence in cortical and DRG neurons

    PMID:28935671

    Open questions at the time
    • Molecular mechanism by which PSD blocks vesicle entry unresolved
    • Role of ARF6 GEF activity in this function not dissected
  11. 2019 High

    Uncovered a GEF-independent activity—the N-terminal MTED directly inhibits microtubule polymerization—and a CD13/IQGAP1-anchored ARF6 complex promoting integrin recycling and migration.

    Evidence In vitro MT polymerization assay, MTED tubulin binding, Drosophila gain/loss-of-function with live MT imaging; co-IP, PLA, knockdown, β1 integrin trafficking and migration assays

    PMID:31040262 PMID:31718774

    Open questions at the time
    • Conservation of mammalian MTED function not fully established
    • Integration of MTED and GEF activities in a single cell context unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PSD's distinct activities—ARF6 GEF catalysis, MTED-mediated microtubule inhibition, and actin remodeling—are coordinated and selectively deployed across epithelial, migratory, and neuronal contexts remains unresolved.
  • No structural model integrating Sec7, PH, MTED, and C-terminal modules
  • Spatial/temporal switching between GEF and microtubule functions undefined
  • In vivo mammalian knockout phenotype not characterized in corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 1
Partners
ALPHA-ACTININ-1ARF6CD13ENDOPHILINIQGAP1TWIK1USP9X

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EFA6A (PSD/EFA6) contains Sec7 and pleckstrin homology (PH) domains and functions as a guanine nucleotide exchange factor (GEF) that promotes efficient GDP/GTP exchange specifically on ARF6 (not ARF1). EFA6A localizes to the cytoplasmic face of plasma membrane invaginations, regulates endosomal membrane recycling and transferrin receptor redistribution to the cell surface, and induces actin-based membrane ruffles dependent on ARF6 and Rac1 activation. GEF nucleotide exchange assays, subcellular localization by immunofluorescence, dominant-negative ARF6 and Rac1 co-expression, transferrin recycling assay The EMBO journal High 10075920
2001 In vitro, EFA6A (PSD) Sec7 domain activates ARF6 exclusively and does not activate ARF1, whereas ARNO activates ARF1 preferentially. Selectivity is determined by the Sec7 domain alone and by the ARF core domains, independent of the myristoylated N-terminal helix. In vitro GEF activity assay on phospholipid membranes with isolated Sec7 domains and ARF core domains; ARF1/ARF6 specificity mapping The Journal of biological chemistry High 11342560
2002 EFA6A (PSD/EFA6) and its paralog EFA6B share a conserved C-terminal ~150 aa region with a predicted coiled-coil motif. Overexpression of the PH domain/C-terminal region of EFA6A or EFA6B (without the Sec7 domain) promotes lengthening of dorsal microvilli-like membrane protrusions, an effect requiring integrity of the coiled-coil motif. Association with membrane ruffles depends on the PH domain, which interacts with PI(4,5)P2. Deletion/domain-swap overexpression in BHK cells, immunofluorescence localization, coiled-coil motif mutagenesis Journal of cell science Medium 12082148
2003 EFA6 (PSD) regulates actin cytoskeleton dynamics and tight junction (TJ) formation in epithelial MDCK cells in response to E-cadherin engagement. EFA6 is recruited to a Triton X-100-insoluble fraction upon calcium-triggered E-cadherin adhesion, selectively stabilizes the apical actin ring to retain occludin at the cell surface and exclude TJ proteins from endocytosis. These effects require both the catalytic Sec7 exchange activity and the actin-remodeling C-terminal domain. Calcium switch assay, Triton X-100 fractionation, immunofluorescence, overexpression of catalytic-dead Sec7 mutant, C-terminal domain deletion constructs Molecular biology of the cell Medium 14668475
2004 EFA6 (PSD) interacts with TWIK1 K+ channel only when EFA6 is bound to ARF6 (ARF6-dependent interaction). TWIK1 is expressed in a subapical recycling endosomal compartment in renal proximal tubules and polarized MDCK cells; the ARF6/EFA6/TWIK1 complex is proposed to regulate channel internalization and recycling. Co-immunoprecipitation, yeast two-hybrid, subcellular localization by immunofluorescence EMBO reports Medium 15540117
2004 EFA6A (PSD) promotes dendritic spine formation in hippocampal neurons in an ARF6 activation-dependent manner. Active ARF6 promotes conversion of filopodia to spines. Knockdown of ARF6 and EFA6A by siRNA decreases spine formation and reduces filopodia-to-spine conversion. ARF6 and EFA6A protect mature spines from inactivity-induced destabilization. The spine-promoting effect of ARF6 is partially blocked by Rac1. siRNA knockdown, dominant-negative ARF6, live-imaging of spine dynamics, overexpression in hippocampal neurons The Journal of neuroscience High 16672654
2004 EFA6A (PSD) mRNA is somatodendritically localized in hippocampal neurons in vivo and in vitro, with peak dendritic expression between P7 and P14 in rats. Overexpression of a GEP-defective (catalytically dead) mutant of EFA6A enhances dendritic formation, implicating EFA6A in regulation of hippocampal dendritic development. Non-radioactive in situ hybridization, overexpression of catalytic-dead EFA6A mutant, morphometric analysis of dendrites The European journal of neuroscience Medium 15009133
2006 EFA6A (PSD) enhances glioma cell invasion through an ARF6/ERK signaling cascade. Overexpression of EFA6A significantly increases cell motility and invasiveness; these effects are abolished by the catalytic-dead EFA6A(E242K) mutant, dominant-negative ARF6(T27N), or the MEK inhibitor U0126, indicating that EFA6A acts upstream of ARF6 to activate ERK-dependent invasion. Conditional overexpression, wound healing and Matrigel invasion assays, dominant-negative EFA6A and ARF6, pharmacological MEK inhibition, phospho-ERK western blot Cancer research Medium 16452216
2006 EFA6D (a family member of EFA6/PSD) shows preferential GEF activity toward ARF6 in ARF pull-down assays and is highly concentrated in the postsynaptic density fraction of mouse brain, with a distinct spatiotemporal expression pattern from EFA6A and EFA6C. ARF pull-down GEF activity assay, subcellular fractionation, RT-PCR, in situ hybridization Brain research Medium 16707115
2007 EFA6A (PSD) protein localizes to dendritic spines of hippocampal neurons and can interact with alpha-actinin-1. Yeast two-hybrid and immunofluorescence co-localization show partial overlap of EFA6A and alpha-actinin at dendritic spines in vivo and in culture. The central region of alpha-actinin-1 (spectrin repeats) mediates the interaction with EFA6A's C-terminal region. Yeast two-hybrid screening, immunofluorescence co-localization in hippocampal neurons, subcellular fractionation The European journal of neuroscience Medium 17298598
2008 EFA6A (PSD) and three other EFA6 family members (EFA6A, EFA6C, EFA6D) are abundantly expressed in mouse brain and enriched in the postsynaptic density fraction, establishing that EFA6 family GEFs for ARF6 are concentrated at neuronal synapses. Subcellular fractionation, immunoblot, RT-PCR, in situ hybridization (review/summary of experimental findings from multiple prior studies) The Tohoku journal of experimental medicine Low 18323689
2010 USP9x-mediated deubiquitination of EFA6 (PSD) is required for tight junction biogenesis. At steady state, EFA6 is constitutively ubiquitinated and degraded by the proteasome. At newly forming epithelial contacts, USP9x deubiquitinates EFA6, leading to a transient increase in EFA6 levels that facilitates TJ formation. Knockdown of either EFA6 or USP9x impairs TJ biogenesis; EFA6 overexpression rescues TJ biogenesis in USP9x-knockdown cells. Knockdown by siRNA, co-immunoprecipitation, overexpression rescue, immunofluorescence co-localization at primordial junctions The EMBO journal High 20339350
2014 EFA6 (PSD) directly interacts with endophilin via the endophilin N-BAR domain (identified by two-hybrid and confirmed with purified proteins). Endophilin stimulates the catalytic GEF activity of EFA6A on ARF6. The Sec7 domain of EFA6A competes with flat (but not highly curved) lipid membranes for N-BAR binding. In cells, EFA6A recruits endophilin to EFA6A-positive plasma membrane ruffles, and endophilin expression rescues EFA6A-mediated inhibition of transferrin internalization, placing EFA6/ARF6 upstream of clathrin-mediated endocytosis. Yeast two-hybrid, in vitro pulldown with purified proteins, GEF activity assay, lipid competition assay, co-localization, transferrin internalization rescue assay Proceedings of the National Academy of Sciences of the United States of America High 24979773
2017 EFA6 (PSD) localizes within the axon initial segment (AIS) of mature CNS cortical neurons and acts as an intrinsic regulator of selective axon transport. EFA6 at the AIS restricts Rab11 vesicle (and integrin) transport into axons. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances axon regeneration after laser axotomy; overexpressing EFA6 prevents DRG neuron regeneration. EFA6 does not localize at the AIS in DRG axons, correlating with their regenerative capacity. siRNA/shRNA knockdown, laser axotomy, live imaging of Rab11/integrin transport, overexpression, localization by immunofluorescence Journal of cell science High 28935671
2019 CD13 tethers EFA6 (PSD) to the plasma membrane at the leading edge of migrating cells, forming a complex with IQGAP1 and active ARF6. This complex promotes ARF6 GTPase cycling, β1 integrin recycling to the surface (preventing its trafficking to late endosomes and degradation), and cell migration. Loss of CD13 impairs EFA6 membrane positioning and reduces ARF6 activity. Co-immunoprecipitation, proximity ligation assay, siRNA knockdown, β1 integrin trafficking assay, migration assays, immunofluorescence Science signaling Medium 31040262
2019 EFA6 (PSD/Drosophila Efa6) can directly inhibit microtubule polymerization at the plasma membrane via an N-terminal 18 amino acid motif (MT elimination domain, MTED) that binds tubulin and inhibits microtubule growth in vitro and in cells, independent of ARF GEF activity. Full-length membrane-anchored Efa6 blocks explorative MTs in axon shafts and growth cones; loss of Efa6 increases explorative MTs leading to increased axon branching and growth, while overexpression causes axon atrophy. In vitro microtubule polymerization assay, MTED peptide binding to tubulin, Drosophila neuron overexpression/loss-of-function, live imaging of MT dynamics, morphometric analysis eLife High 31718774

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science (New York, N.Y.) 1641 7569905
2000 PSD-95 involvement in maturation of excitatory synapses. Science (New York, N.Y.) 964 11082065
2012 Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Molecular oral microbiology 883 23134607
1997 Binding of neuroligins to PSD-95. Science (New York, N.Y.) 610 9278515
2007 The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron 459 17329211
2003 Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 458 14642282
2004 Identification of PSD-95 palmitoylating enzymes. Neuron 452 15603741
2004 A balance between excitatory and inhibitory synapses is controlled by PSD-95 and neuroligin. Proceedings of the National Academy of Sciences of the United States of America 293 15358863
2003 PSD-95 regulates synaptic transmission and plasticity in rat cerebral cortex. The Journal of physiology 257 12563010
1999 EFA6, a sec7 domain-containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization. The EMBO journal 251 10075920
2011 PSD-95 is required to sustain the molecular organization of the postsynaptic density. The Journal of neuroscience : the official journal of the Society for Neuroscience 250 21525273
2015 PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density. Proceedings of the National Academy of Sciences of the United States of America 243 26604311
2007 Synaptic accumulation of PSD-95 and synaptic function regulated by phosphorylation of serine-295 of PSD-95. Neuron 230 17988632
2014 Role of the DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 in schizophrenia. PloS one 206 24416398
2012 PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nature neuroscience 206 22246437
2016 Identification of PSD-95 Depalmitoylating Enzymes. The Journal of neuroscience : the official journal of the Society for Neuroscience 193 27307232
2008 Differential trafficking of AMPA and NMDA receptors by SAP102 and PSD-95 underlies synapse development. Proceedings of the National Academy of Sciences of the United States of America 185 19104036
2007 PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. The Journal of neuroscience : the official journal of the Society for Neuroscience 179 17855605
2011 Regulation of AMPA receptor surface diffusion by PSD-95 slots. Current opinion in neurobiology 177 22051694
2000 PSD-95 and SAP97 exhibit distinct mechanisms for regulating K(+) channel surface expression and clustering. The Journal of cell biology 157 10629225
2013 Impairment of TrkB-PSD-95 signaling in Angelman syndrome. PLoS biology 147 23424281
2011 PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs) and synaptic plasticity. Current opinion in neurobiology 145 21450454
2008 PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling. The Journal of cell biology 144 19075115
2008 Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. The Journal of physiology 133 18936077
1993 Cloning of a gene (PSD1) encoding phosphatidylserine decarboxylase from Saccharomyces cerevisiae by complementation of an Escherichia coli mutant. The Journal of biological chemistry 124 8227017
1999 Identification of an intramolecular interaction between the SH3 and guanylate kinase domains of PSD-95. The Journal of biological chemistry 121 10364172
2021 PSD-95 protects synapses from β-amyloid. Cell reports 119 34077732
2013 Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression. The Journal of neuroscience : the official journal of the Society for Neuroscience 115 23864697
2001 Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression. The Biochemical journal 115 11368788
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 111 21543610
2012 PSD-95 expression controls L-DOPA dyskinesia through dopamine D1 receptor trafficking. The Journal of clinical investigation 108 23041629
2002 Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95. The Journal of biological chemistry 106 11805122
2016 PSD-95 stabilizes NMDA receptors by inducing the degradation of STEP61. Proceedings of the National Academy of Sciences of the United States of America 103 27457929
2019 PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment. Scientific reports 102 31263190
2006 PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating. Proceedings of the National Academy of Sciences of the United States of America 99 17179037
2005 mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression. Nature cell biology 99 16299499
2006 ARF6 and EFA6A regulate the development and maintenance of dendritic spines. The Journal of neuroscience : the official journal of the Society for Neuroscience 91 16672654
2012 Phosphatidylserine decarboxylase 1 (Psd1) promotes mitochondrial fusion by regulating the biophysical properties of the mitochondrial membrane and alternative topogenesis of mitochondrial genome maintenance protein 1 (Mgm1). The Journal of biological chemistry 87 23045528
2009 Neuroligin1: a cell adhesion molecule that recruits PSD-95 and NMDA receptors by distinct mechanisms during synaptogenesis. Neural development 87 19450252
2002 A conserved C-terminal domain of EFA6-family ARF6-guanine nucleotide exchange factors induces lengthening of microvilli-like membrane protrusions. Journal of cell science 86 12082148
2003 Production of the active antifungal Pisum sativum defensin 1 (Psd1) in Pichia pastoris: overcoming the inefficiency of the STE13 protease. Protein expression and purification 84 12963348
2003 Interactions between Src family protein tyrosine kinases and PSD-95. Neuropharmacology 82 14529711
2001 The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. The Journal of biological chemistry 82 11278603
2013 PSD-95 promotes the stabilization of young synaptic contacts. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 73 24298137
2022 Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners. International journal of molecular sciences 72 35457207
2016 Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. Molecular neurobiology 71 26884267
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
2004 ARF6-dependent interaction of the TWIK1 K+ channel with EFA6, a GDP/GTP exchange factor for ARF6. EMBO reports 66 15540117
2011 The PSD-95/nNOS complex: new drugs for depression? Pharmacology & therapeutics 65 22133842
2010 Postsynaptic clustering and activation of Pyk2 by PSD-95. The Journal of neuroscience : the official journal of the Society for Neuroscience 65 20071509
2014 Durable fear memories require PSD-95. Molecular psychiatry 64 25510511
2018 α-Actinin Anchors PSD-95 at Postsynaptic Sites. Neuron 63 29429936
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
2001 Specificities for the small G proteins ARF1 and ARF6 of the guanine nucleotide exchange factors ARNO and EFA6. The Journal of biological chemistry 62 11342560
2022 O-GlcNAcylation modulates liquid-liquid phase separation of SynGAP/PSD-95. Nature chemistry 61 35637289
2021 PSD-95: An Effective Target for Stroke Therapy Using Neuroprotective Peptides. International journal of molecular sciences 60 34830481
2015 Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3. Nature neuroscience 59 26479588
2013 Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons. Molecular and cellular neurosciences 59 23932971
2017 Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs. Cell reports 58 29281827
1993 The pss and psd genes are required for motility and chemotaxis in Escherichia coli. Journal of bacteriology 57 8244943
2011 Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 21849563
2006 PSD-95 is a negative regulator of the tyrosine kinase Src in the NMDA receptor complex. The EMBO journal 54 16990796
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
2013 The PSD protein ProSAP2/Shank3 displays synapto-nuclear shuttling which is deregulated in a schizophrenia-associated mutation. Experimental neurology 51 24382453
2010 USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly. The EMBO journal 51 20339350
2003 EFA6, exchange factor for ARF6, regulates the actin cytoskeleton and associated tight junction in response to E-cadherin engagement. Molecular biology of the cell 51 14668475
2008 Postsynaptic density-membrane associated guanylate kinase proteins (PSD-MAGUKs) and their role in CNS disorders. Neuroscience 50 18773944
2001 cDNA cloning and heterologous expression of functional cysteine-rich antifungal protein Psd1 in the yeast Pichia pastoris. Archives of biochemistry and biophysics 50 11697857
2008 Distribution of the scaffolding proteins PSD-95, PSD-93, and SAP97 in isolated PSDs. Brain cell biology 49 18392731
2019 Postsynaptic density protein 95 (PSD-95) is transported by KIF5 to dendritic regions. Molecular brain 48 31753031
2008 Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 19118189
2017 Psd1 Effects on Candida albicans Planktonic Cells and Biofilms. Frontiers in cellular and infection microbiology 46 28649561
2005 Differential expression of two NMDA receptor interacting proteins, PSD-95 and SynGAP during mouse development. The European journal of neuroscience 44 15673435
2005 The scaffolding protein PSD-95 interacts with the glycine transporter GLYT1 and impairs its internalization. Journal of neurochemistry 44 16271045
1999 Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family. Brain research. Molecular brain research 44 10521598
2016 D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability. Frontiers in cellular neuroscience 42 26941605
2009 Alterations of NR2B and PSD-95 expression in hippocampus of kainic acid-exposed rats with behavioural deficits. Behavioural brain research 41 19428647
2006 Distinct spatiotemporal expression of EFA6D, a guanine nucleotide exchange factor for ARF6, among the EFA6 family in mouse brain. Brain research 40 16707115
2019 CD13 tethers the IQGAP1-ARF6-EFA6 complex to the plasma membrane to promote ARF6 activation, β1 integrin recycling, and cell migration. Science signaling 39 31040262
2014 Epigenetic upregulation of PSD-95 contributes to the rewarding behavior by morphine conditioning. European journal of pharmacology 38 24704371
2006 EFA6A enhances glioma cell invasion through ADP ribosylation factor 6/extracellular signal-regulated kinase signaling. Cancer research 37 16452216
2004 Somatodendritic localization of the mRNA for EFA6A, a guanine nucleotide exchange protein for ARF6, in rat hippocampus and its involvement in dendritic formation. The European journal of neuroscience 37 15009133
2017 EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment. Journal of cell science 36 28935671
2017 Ca2+/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down. The EMBO journal 35 29118000
2016 Functional characterization of the Aspergillus nidulans glucosylceramide pathway reveals that LCB Δ8-desaturation and C9-methylation are relevant to filamentous growth, lipid raft localization and Psd1 defensin activity. Molecular microbiology 35 27479571
2023 Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density. Nature communications 34 37891164
2022 Fuzzy supertertiary interactions within PSD-95 enable ligand binding. eLife 34 36069777
2018 PSD-95-nNOS Coupling Regulates Contextual Fear Extinction in the Dorsal CA3. Scientific reports 34 30143658
2012 Evaluation of the membrane lipid selectivity of the pea defensin Psd1. Biochimica et biophysica acta 33 22373959
2014 Arf6 exchange factor EFA6 and endophilin directly interact at the plasma membrane to control clathrin-mediated endocytosis. Proceedings of the National Academy of Sciences of the United States of America 31 24979773
2013 The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological synapse. Pflugers Archiv : European journal of physiology 31 23553419
2007 Somatodendritic localization of EFA6A, a guanine nucleotide exchange factor for ADP-ribosylation factor 6, and its possible interaction with alpha-actinin in dendritic spines. The European journal of neuroscience 31 17298598
2006 SPIN90/WISH interacts with PSD-95 and regulates dendritic spinogenesis via an N-WASP-independent mechanism. The EMBO journal 31 16990791
2018 Wnt-7a Stimulates Dendritic Spine Morphogenesis and PSD-95 Expression Through Canonical Signaling. Molecular neurobiology 30 29967987
2019 Csmd2 Is a Synaptic Transmembrane Protein that Interacts with PSD-95 and Is Required for Neuronal Maturation. eNeuro 28 31068362
2019 Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex. eLife 28 31718774
2020 PSD-95 deficiency alters GABAergic inhibition in the prefrontal cortex. Neuropharmacology 27 32818520
2013 Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses. PloS one 27 23342049
2008 The EFA6 family: guanine nucleotide exchange factors for ADP ribosylation factor 6 at neuronal synapses. The Tohoku journal of experimental medicine 27 18323689

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