Affinage

NSF

Vesicle-fusing ATPase · UniProt P46459

Length
744 aa
Mass
82.6 kDa
Annotated
2026-06-10
100 papers in source corpus 56 papers cited in narrative 56 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NSF (yeast SEC18) is a hexameric AAA+ ATPase that serves as the universal engine for recycling SNARE proteins after membrane fusion, originally defined as an essential factor for secretory transport between the ER, Golgi, and cell surface (PMID:3054509, PMID:2071670). It operates with soluble NSF attachment proteins (alpha-, beta-, gamma-SNAP; yeast Sec17p), which recruit NSF to membranes, bind the SNARE substrate, and stimulate its ATPase activity by lowering the Km of the low-affinity catalytic site, thereby acting as a molecular switch (PMID:2111733, PMID:8455721, PMID:7961908, PMID:9362506). Structurally, NSF is a hollow nucleotide-stabilized hexamer whose D1 ring engages the assembled cis-SNARE complex within an asymmetric '20S' particle; disassembly is initiated by a conserved 1:1 alpha-SNAP:SNARE interaction, after which the N-terminus of SNAP-25 is loaded into the D1 pore prior to ATP hydrolysis (PMID:9267032, PMID:9624162, PMID:22307055, PMID:23836889, PMID:30198481). NSF couples ATP hydrolysis to dissociation through the SNARE ionic layer and executes disassembly of a single complex in one 'spring-loaded' burst within ~20 ms (PMID:11762430, PMID:25814585). This activity recycles SDS-resistant cis-SNARE cores formed by syntaxin/SNAP-25/synaptobrevin (PMID:7588600, PMID:9852562), while trans-SNARE complexes (SNAREpins) become resistant to NSF at the moment of formation, allowing fusion to proceed; this protection is reinforced by Munc18-1, Munc13-1, complexin-1, and synaptotagmin-1 (PMID:10831610, PMID:29985126, PMID:30657450). Genetic studies in Drosophila and squid place NSF action after vesicle docking, priming docked vesicles for calcium-triggered release rather than catalyzing fusion itself (PMID:9852562, PMID:9852561, PMID:9469810, PMID:11593041). NSF supports a broad range of fusion events, including Golgi reassembly, basolateral TGN-to-plasma-membrane transport, homotypic vacuole fusion, late endosome-lysosome fusion, and autophagosome-vacuole fusion (PMID:7758111, PMID:7553851, PMID:8670830, PMID:9456319, PMID:11694599); at the Golgi it additionally has an ATPase-independent function in which NSF/alpha-SNAP catalyze GATE-16 binding to the v-SNARE GOS-28 (PMID:12070132, PMID:14617820). Beyond SNAREs, NSF directly binds the AMPA receptor GluR2 subunit and, using its ATPase, disassembles the inhibitory GluR2-PICK1 complex to stabilize surface AMPA receptors and maintain synaptic transmission (PMID:9697854, PMID:10399941, PMID:11931741, PMID:12441055); it also binds beta-arrestin1 to promote receptor internalization and the GABAB receptor heterodimer to prime agonist-induced desensitization (PMID:10196135, PMID:16724110). NSF activity is post-translationally tuned by LRRK2 phosphorylation at Thr645, which enhances its ATPase rate and SNARE disassembly (PMID:26758690).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1988 High

    Established that NSF/SEC18 is an essential, cytoplasmic factor for secretory transport, framing the central question of how a soluble ATPase drives membrane traffic.

    Evidence Gene cloning by complementation and disruption in yeast with subcellular fractionation

    PMID:3054509

    Open questions at the time
    • Molecular substrate of NSF unknown
    • Mechanism of membrane association undefined
  2. 1990 High

    Identified SNAP adaptors that bridge NSF to membranes, defining the conserved NSF/SNAP fusion machinery across species.

    Evidence Protein purification from brain cytosol, in vitro Golgi transport assay, yeast sec17 complementation

    PMID:2111733

    Open questions at the time
    • Membrane receptor for the SNAP-NSF complex not yet identified
    • Catalytic role of NSF ATPase unresolved
  3. 1993 High

    Showed SNAP isoforms act through membrane-specific SNARE receptors, introducing the concept that fusion specificity is encoded downstream of NSF.

    Evidence cDNA cloning, in vitro Golgi transport, tissue expression analysis

    PMID:8455721

    Open questions at the time
    • Identity of the relevant SNARE receptors at each step incomplete
  4. 1994 High

    Defined SNAPs as activators that lower NSF's ATPase Km ~100-fold, establishing them as a molecular switch for NSF activity at physiological ATP.

    Evidence In vitro ATPase kinetics with recombinant NSF and SNAPs

    PMID:7961908

    Open questions at the time
    • How ATP hydrolysis is coupled to a downstream conformational event not yet shown
  5. 1995 High

    Resolved NSF architecture and the 20S complex, showing alpha-SNAP and the SNARE rod bind one end of the NSF cylinder, and identified the SDS-resistant SNARE core as the physiological substrate.

    Evidence Quick-freeze/deep-etch EM with epitope markers; in vitro 20S assembly/disassembly with neurotoxin cleavage

    PMID:7588600 PMID:9267032

    Open questions at the time
    • Oligomeric state ambiguous at this stage
    • Atomic contacts within the 20S particle unresolved
  6. 1997 High

    Established NSF as a nucleotide-stabilized hexamer and mapped the alpha-SNAP C-terminus as the determinant required to stimulate NSF ATPase and thereby drive SNARE disassembly and exocytosis.

    Evidence Analytical ultracentrifugation and EM; alpha-SNAP truncation/point mutants in ATPase, disassembly, and chromaffin exocytosis assays

    PMID:8744944 PMID:9325254 PMID:9362506 PMID:9624162

    Open questions at the time
    • Whether NSF acts before or after fusion not yet ordered
    • Non-SNARE substrates not yet considered
  7. 1998 High

    Genetic and physiological studies in Drosophila and squid placed NSF action downstream of vesicle docking, priming docked vesicles rather than catalyzing fusion.

    Evidence comatose temperature-sensitive mutants with SNARE accumulation, EM, and NMJ electrophysiology; squid presynaptic peptide injection

    PMID:9469810 PMID:9852561 PMID:9852562

    Open questions at the time
    • Whether SNARE disassembly precedes or follows fusion not definitively ordered until later epistasis
  8. 1998 High

    Discovered the first non-SNARE NSF partner, the AMPA receptor GluR2 subunit, linking NSF directly to synaptic receptor trafficking and transmission.

    Evidence Direct binding with peptide mapping/mutagenesis; blocking peptide and antibody infusion in CA1 neurons with electrophysiology

    PMID:9697854 PMID:9697855

    Open questions at the time
    • Mechanism by which NSF acts on GluR2 (disassembly of what complex) unknown at this point
  9. 1998 High

    Extended NSF requirement to homotypic vacuole fusion and late endosome-lysosome fusion as direct fusion events, defining an ordered priming reaction coupled to t-SNARE stabilization via LMA1.

    Evidence Cell-free vacuole and endosome-lysosome fusion assays with purified Sec18p, antibodies, and LMA1 transfer experiments

    PMID:8670830 PMID:9015301 PMID:9456319 PMID:9657146

    Open questions at the time
    • Lipid and cofactor requirements of priming not fully mapped
  10. 1999 High

    Demonstrated NSF-GluR2 interaction maintains surface AMPA receptors and is required for LTD-related receptor pools, and identified beta-arrestin1 as an ATP-state-dependent NSF partner in receptor internalization.

    Evidence Blocking peptide/viral pep2m in neurons with electrophysiology and surface immunostaining; yeast two-hybrid, co-IP, and HEK293 internalization assays

    PMID:10196135 PMID:10399941 PMID:10571232

    Open questions at the time
    • Molecular substrate of the NSF-GluR2 reaction still undefined
    • beta-arrestin1 finding is Co-IP/two-hybrid without mechanistic dissection
  11. 2000 High

    Resolved how fusion proceeds despite NSF: trans-SNARE complexes become NSF-resistant at the moment of formation, while cis-SNARE complexes are dismantled.

    Evidence Reconstituted liposome fusion with NSF/alphaSNAP applied to trans- vs cis-SNARE complexes

    PMID:10831610

    Open questions at the time
    • Factors actively protecting trans-SNARE complexes not yet identified
  12. 2001 High

    Identified the GluR2-PICK1 complex as the first non-SNARE substrate of NSF's ATPase-driven disassembly and established the ionic layer as the coupling element for disassembly.

    Evidence In vitro ATPgammaS/ATP disassembly assays with GluR2-PICK1 and SNARE ionic-layer mutants; SNAP overexpression in neurons

    PMID:11483507 PMID:11593041 PMID:11762430 PMID:11931741

    Open questions at the time
    • How NSF discriminates SNARE vs non-SNARE substrates unresolved
  13. 2002 High

    Revealed an ATPase-independent NSF function essential for Golgi membrane fusion and separated NSF-dependent receptor stabilization from AP2-dependent internalization in synaptic plasticity.

    Evidence G274E/comatose NSF mutants in Golgi reassembly and GATE-16/GOS-28 binding; GluR2 separation-of-function mutants in internalization and LTD assays

    PMID:12011465 PMID:12070132 PMID:12441055

    Open questions at the time
    • Structural basis of the ATPase-independent Golgi activity unknown
  14. 2003 High

    Distinguished NSF from the related ATPase p97 as the factor directly required for Golgi membrane fusion in cells.

    Evidence Dominant-negative NSF(E329Q) vs p97(E578Q) expression with Golgi morphology and transport readouts

    PMID:14617820

    Open questions at the time
    • Division of labor between NSF and p97 at other organelles not addressed
  15. 2006 Medium

    Expanded NSF's direct receptor partnerships to the GABAB receptor heterodimer and showed a cell-autonomous neuronal role in node-of-Ranvier organization independent of synaptic vesicle fusion.

    Evidence Co-IP from synaptosomes/CHO cells with TAT-peptide inhibition and signaling readouts; zebrafish forward genetics with chimeric transplantation

    PMID:16581508 PMID:16724110

    Open questions at the time
    • GABAB finding from single lab without structural definition of interaction
    • Mechanism linking NSF to sodium channel clustering unknown
  16. 2009 High

    Mapped a membrane-attachment loop in alpha-SNAP required specifically for disassembly of membrane-bound SNARE complexes, connecting SNAP membrane contact to NSF function.

    Evidence In vitro disassembly comparing soluble vs membrane-bound SNAREs with alpha-SNAP phenylalanine mutants

    PMID:19762473

    Open questions at the time
    • Contribution of this loop to in vivo fusion cycles not directly tested here
  17. 2013 High

    Defined the universal initiation step of disassembly as a conserved 1:1 alpha-SNAP:SNARE interaction independent of N-terminal SNARE domains, with NSF binding thereafter.

    Evidence Kinetic and multiangle light scattering analysis across four SNARE complexes

    PMID:23836889

    Open questions at the time
    • Stoichiometry of alpha-SNAP in the active 20S particle later revised to two
  18. 2015 High

    Established the kinetic mechanism (single-complex disassembly in one spring-loaded burst within 20 ms) and uncovered a SNARE-disassembly-independent role for Sec17 in directly triggering trans-SNARE fusion.

    Evidence Single-molecule fluorescence and magnetic tweezers; proteoliposome fusion with Sec17/Sec18 separation-of-function mutants

    PMID:25814585 PMID:25902545

    Open questions at the time
    • Atomic-resolution view of substrate loading still pending
  19. 2016 High

    Identified LRRK2 phosphorylation of NSF at Thr645 as a post-translational regulator that enhances ATPase activity and SNARE disassembly rate.

    Evidence In vitro kinase assay, phosphosite mapping, T645A mutagenesis, ATPase and disassembly assays

    PMID:26758690

    Open questions at the time
    • Physiological/in vivo consequence of NSF Thr645 phosphorylation not established
  20. 2018 High

    Near-atomic cryo-EM of the 20S supercomplex resolved two alpha-SNAP molecules contacting the SNARE complex and the SNAP-25A N-terminus loaded into the D1 pore before hydrolysis, defining the substrate-engagement mechanism; single-molecule work showed complexin competes with alpha-SNAP and NSF can disassemble anti-parallel complexes for quality control.

    Evidence Cryo-EM of the 20S supercomplex at ~3.9 A; single-molecule FRET with complexin-1 competition

    PMID:29985126 PMID:30198481

    Open questions at the time
    • Dynamics of pore translocation during the hydrolysis burst not fully captured
  21. 2019 High

    Identified the accessory factors (Munc18-1, Munc13-1, complexin-1, synaptotagmin-1) that build and protect trans-SNARE complexes against NSF-alphaSNAP de-priming, integrating NSF into the priming/fusion cycle.

    Evidence Reconstituted proteoliposome system with defined components, co-flotation/co-sedimentation assays

    PMID:30657450

    Open questions at the time
    • Quantitative competition between protection and NSF disassembly in vivo unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NSF achieves substrate selectivity between SNARE and diverse non-SNARE targets, and how its phosphoregulation and accessory-factor protection are integrated in vivo, remains open.
  • No unified model for substrate recognition across SNARE and non-SNARE clients
  • In vivo regulatory role of LRRK2 phosphorylation undefined
  • Structural basis of ATPase-independent Golgi function unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140657 ATP-dependent activity 4 GO:0016787 hydrolase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005794 Golgi apparatus 4 GO:0005773 vacuole 3 GO:0005886 plasma membrane 3 GO:0005829 cytosol 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 2 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 1
Partners
ARRB1GABBR1GRIA2LRRK2NAPAPICK1PLK2STX5
Complex memberships
20S SNARE disassembly complex (NSF/alphaSNAP/SNARE)NSF homohexamer

Evidence

Reading pass · 56 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 SEC18 (yeast NSF) is essential for yeast cell growth and is required for secretory protein transport between the ER and Golgi complex. The protein is hydrophilic, lacks signal sequence or transmembrane anchor, resides in the cytoplasm, and associates transiently with a 100,000 x g pellet fraction consistent with small vesicles. Gene cloning by complementation, gene disruption, subcellular fractionation, in vitro transcription/translation Molecular and cellular biology High 3054509
1990 Three soluble NSF attachment proteins (alpha-, beta-, gamma-SNAP) were purified from bovine brain cytosol and shown to bind NSF to Golgi membranes, forming a SNAP-NSF-membrane complex required for the membrane fusion stage of intra-Golgi transport. Yeast SEC17 encodes a functional homolog of alpha-SNAP, establishing evolutionary conservation of the NSF/SNAP fusion mechanism. Protein purification, in vitro Golgi transport assay, complementation with yeast sec17 mutant cytosol Cell High 2111733
1991 Yeast Sec18p/NSF function is required sequentially for protein transport from the ER to the Golgi, through multiple Golgi compartments, and from the Golgi to the cell surface, defining at least three functionally distinct Golgi compartments. Temperature-shift experiments with sec18 and sec23 yeast mutants tracking transport of alpha-factor and CPY biosynthetic intermediates The Journal of cell biology High 2071670
1992 NSF and alpha-SNAP are required during the formation of functional transport vesicles from Golgi membranes, not only at the attachment/fusion step; after vesicle formation, the NEM-sensitive function of NSF is no longer required. Cell-free Golgi transport assay measuring functional vesicle formation; immunodepletion of NSF/SNAP The Journal of cell biology Medium 1522110
1993 Alpha- and gamma-SNAP are ubiquitously expressed and act synergistically in intra-Golgi transport; beta-SNAP is a brain-specific isoform of alpha-SNAP. SNAPs enable NSF to bind to target membranes, and their action at specific fusion sites is controlled by SNARE receptors particular to the membranes being fused. cDNA cloning, in vitro Golgi transport assay, tissue expression analysis Nature High 8455721
1994 NSF ATPase activity is regulated by alpha- and gamma-SNAPs. Immobilized (but not soluble) SNAPs enhance NSF ATPase activity in a dose-dependent manner, primarily by decreasing the Km of the low-affinity ATPase site ~100-fold, thereby acting as a molecular switch to activate NSF at physiological ATP concentrations. In vitro ATPase assay with recombinant His6-tagged NSF and SNAPs; enzyme kinetics analysis The Journal of biological chemistry High 7961908
1995 NSF mediates basolateral (but not apical) transport from the trans-Golgi network to the plasma membrane in MDCK epithelial cells. Anti-NSF antibodies and alpha-SNAP inhibit/stimulate basolateral transport, while apical transport is insensitive to NSF, Rab-GDI, and neurotoxins. In vitro transport assay with streptolysin O-permeabilized MDCK cells; anti-NSF antibodies; toxin inhibition Cell High 7758111
1995 NSF together with SNAPs and p115 (a vesicle docking protein) restores cisternal regrowth from mitotic Golgi fragments in a cell-free system, while p97 (an NSF-like ATPase) also restores regrowth but produces morphologically distinct cisternae, indicating distinct roles in rebuilding Golgi after mitosis. Cell-free Golgi reassembly assay; NEM or salt-washing inhibition; reconstitution with purified proteins Cell High 7553851
1995 Alpha- and gamma-SNAP stimulate Ca2+-dependent exocytosis in digitonin-permeabilized chromaffin cells. Recombinant NSF alone was ineffective, but ~1/3 of cellular NSF is in a non-cytosolic form sufficient for exocytosis. The stimulatory effect of alpha-SNAP requires Ca2+, MgATP, and is blocked by NEM and botulinum A toxin. Permeabilized chromaffin cell exocytosis assay; recombinant protein addition; inhibitor analysis The EMBO journal High 7835334
1995 NSF is a hollow 10×16 nm cylindrical oligomeric ATPase. Without nucleotide, NSF adopts a 'splayed' protease-sensitive conformation revealing its subunit composition. The ternary SNARE complex (syntaxin/SNAP-25/synaptobrevin) forms a 4×14 nm rod with syntaxin and synaptobrevin aligned in parallel with membrane anchors at the same end. Alpha-SNAP and the SNARE rod bind to one end of the NSF cylinder forming an asymmetric '20S' complex. Quick-freeze/deep-etch electron microscopy; epitope tags; antibody and maltose-binding protein markers on recombinant proteins Cell High 9267032
1995 A clostridial neurotoxin-sensitive SDS-resistant SNARE core (synaptobrevin/syntaxin/SNAP-25) is the physiological target for NSF-mediated ATP-dependent disassembly in the presence of SNAP. Cleavage of synaptobrevin or SNAP-25 by neurotoxins does not prevent 20S complex assembly but compromises the stability of the SDS-resistant SNARE core. In vitro 20S complex assembly/disassembly assay; clostridial neurotoxin cleavage; gel shift analysis The EMBO journal High 7588600
1996 NSF is required for homotypic vacuole fusion in vitro. Using purified recombinant Sec18p (NSF) and affinity-purified anti-Sec17p (alpha-SNAP) antibodies, both Sec17p and Sec18p are shown to be essential for the homotypic fusion step of vacuole inheritance. Vacuole-to-vacuole fusion is also stimulated by certain fatty acyl-CoA compounds in a Sec18p-dependent manner. Cell-free vacuole inheritance assay; purified recombinant proteins; affinity-purified antibodies The EMBO journal High 8670830
1996 C-terminal deletion of alpha-SNAP abolishes NSF binding, while N-terminal deletions (up to 120 residues) do not prevent NSF binding or ATPase stimulation. Both N- and C-terminal domains of alpha-SNAP are required for syntaxin binding and exocytosis stimulation, placing NSF and syntaxin in proximity through alpha-SNAP. Alpha-SNAP deletion mutant analysis; NSF ATPase assay; permeabilized chromaffin cell exocytosis assay Molecular biology of the cell High 8744944
1997 NSF requires the C-terminal region of alpha-SNAP for ATPase stimulation: deletion of as few as 10 C-terminal residues markedly decreases ATPase stimulation; mutation of conserved leucine 294 to alanine (L294A) reduces ATPase stimulation without affecting NSF binding. Alpha-SNAP mutants defective in stimulating NSF ATPase fail to disassemble the 20S complex or stimulate exocytosis, demonstrating that alpha-SNAP-stimulated NSF ATPase activity is required for SNARE complex disassembly and exocytosis. Alpha-SNAP truncation and point mutants; in vitro ATPase assay; 20S complex disassembly assay; permeabilized chromaffin cell exocytosis assay The Journal of cell biology High 9362506
1997 NSF is a hexamer (not tetramer or trimer) in the presence of nucleotide, stabilized by D2 domain oligomerization. The sedimentation coefficient is 13.4 S, and the unusual hydrodynamic properties cannot be explained by shape alone. Sedimentation equilibrium and velocity analytical ultracentrifugation; transmission EM with rotational image analysis; scanning transmission EM; multiangle light scattering The Journal of biological chemistry High 9624162
1997 NSF and alpha-SNAP mediate dissociation of the Golgi SNARE complex containing GS28 and syntaxin 5. ATP hydrolysis by NSF is required; neither alpha-SNAP nor NSF alone dissociates the complex. Upon dissociation, GS28 (but not syntaxin 5) binds immobilized alpha-SNAP. Coimmunoprecipitation of endogenous Golgi proteins; in vitro disassembly assay with ATP/ATPgammaS; pulldown with immobilized alpha-SNAP The Journal of biological chemistry High 9325254
1997 LMA1 (a heterodimer of thioredoxin and IB2) requires Sec18p (NSF) for high-affinity binding to vacuoles. The Sec18p 'priming' ATPase requires both Sec17p and LMA1. Upon Sec18p ATP hydrolysis, LMA1 transfers to and stabilizes the Vam3p (t-SNARE) complex, coupling priming to t-SNARE stabilization. Cell-free vacuole fusion assay; genetic synthetic lethality; subcellular fractionation; biochemical binding assays The Journal of cell biology High 9015301
1997 Sec18p (NSF) is required for a novel complex at the Golgi-to-endosome (VPS) transport step in yeast. Pep12p (endosomal t-SNARE) affinity chromatography identified Vac1p, Vps45p, and Sec18p as binding partners; sec18-1 combined with overexpression of a dominant pep12 allele caused synthetic growth defects rescued by deletion of PEP12 or VAC1. Affinity chromatography (Pep12p-sepharose); genetic epistasis; temperature-sensitive mutant analysis; subcellular fractionation Molecular biology of the cell High 9201718
1998 NSF interacts directly and selectively with the intracellular C-terminal domain of the AMPA receptor GluR2 subunit (residues Lys-844–Gln-853, with Asn-851 critical), requiring all three domains of NSF. Loading blocking decapeptides corresponding to the NSF-binding domain of GluR2, or an anti-NSF antibody, into CA1 neurons progressively decremented AMPA receptor-mediated synaptic transmission. Direct binding assay, peptide mapping with mutagenesis, intracellular infusion of blocking peptides and antibody in hippocampal CA1 neurons, electrophysiology Neuron High 9697854
1998 GluR2 C-terminal peptide forms an ATP hydrolysis-reversible complex with NSF and alpha-/beta-SNAPs, resembling the SNARE-NSF-SNAP complex assembly. The molar ratio of NSF to SNAP in the GluR2-NSF-SNAP complex is similar to that in the t-SNARE syntaxin-NSF-SNAP complex. Pulldown assay with GluR2 C-terminal peptide; co-immunoprecipitation; immunofluorescence colocalization; ATPgammaS/ATP comparison Neuron High 9697855
1998 In the Drosophila comatose (dNSF-1) mutant, an SDS-resistant neural SNARE complex (syntaxin/n-synaptobrevin/SNAP-25) accumulates at restrictive temperature, predominantly in plasma membrane and docked synaptic vesicle fractions. This establishes that NSF functions to disassemble or rearrange SNARE complexes after vesicle docking to maintain the readily releasable pool. SDS-PAGE of SNARE complexes in Drosophila NSF temperature-sensitive mutant; subcellular fractionation; electrophysiology The Journal of neuroscience High 9852562
1998 NSF functions in Drosophila neuromuscular synapses downstream of vesicle docking to prime docked vesicles for calcium-triggered fusion. In comatose (dNSF-1) mutants at restrictive temperature, progressive activity-dependent reduction in neurotransmitter release occurs with marked accumulation of docked vesicles, indicating NSF does not directly catalyze fusion but maintains the pool of fusion-competent vesicles. Electrophysiology at adult Drosophila neuromuscular junctions; transmission electron microscopy; temperature-sensitive comatose mutant analysis The Journal of neuroscience High 9852561
1998 Injection of peptides inhibiting alpha-SNAP-stimulated NSF ATPase activity into the giant squid presynaptic terminal reduces the amount and slows the kinetics of neurotransmitter release, acting at a step subsequent to vesicle docking and requiring vesicle turnover. Peptide injection into squid giant presynaptic terminal; electrophysiology Science High 9469810
1998 LMA1 binds to vacuoles in a Sec18p-dependent manner, and Sec18p priming ATPase requires both Sec17p and LMA1. Upon Sec18p ATP hydrolysis, LMA1 transfers to a Vam3p (t-SNARE) complex and is later released in a phosphatase-regulated step, coupling the priming reaction to t-SNARE stabilization. Cell-free vacuole fusion assay; protein-membrane binding assays; mutant analysis Cell High 9657146
1998 Late endosome-lysosome fusion is an NSF-dependent direct fusion event (not vesicular transport) that also requires a Rab GTPase. Hybrid organelles formed by this fusion can be isolated from rat liver homogenates confirming the reaction occurs in vivo. Cell-free content mixing assay with rat liver endosomes and lysosomes; NEM inhibition; GDP-dissociation inhibitor; density gradient fractionation; immunoEM The Journal of cell biology High 9456319
1999 NSF identifies beta-arrestin1 as a binding partner (identified by yeast two-hybrid, confirmed by in vitro binding and co-immunoprecipitation). Beta-arrestin1 preferentially interacts with the ATP-bound form of NSF. NSF overexpression enhances agonist-mediated beta2-adrenergic receptor internalization and rescues dominant-negative beta-arrestin1-mediated inhibition of internalization. Yeast two-hybrid screen; in vitro binding of purified recombinant proteins; co-immunoprecipitation; overexpression in HEK293 cells; receptor internalization assay The Journal of biological chemistry Medium 10196135
1999 Disruption of NSF-GluR2 interaction by infusion of blocking peptide (pep2m) into cultured hippocampal neurons reduces surface expression of GluR2-containing AMPA receptors (shown by reduced mEPSC frequency and reduced surface GluR2 immunostaining) without changing total GluR2. NMDA receptor surface expression is unaffected. Blocking peptide infusion into cultured hippocampal neurons; whole-cell patch-clamp; immunostaining with surface vs. total GluR2 comparison; viral expression of pep2m Neuron High 10399941
1999 Alpha-SNAP and NSF are required at an early priming step in chromaffin cell exocytosis before release of readily releasable vesicles. Alpha-SNAP increases the amplitude of both the exocytotic burst and the slow secretion component without changing fusion kinetics, while NEM only partially inhibits the slow component without altering the exocytotic burst. Flash photolysis of caged Ca2+ combined with high-time-resolution capacitance measurement and amperometry; alpha-SNAP and NEM treatments The EMBO journal High 10369670
1999 Blockade of NSF-GluR2 interaction prevents homosynaptic LTD in hippocampal CA1 region. Saturation of LTD prevents pep2m-induced reduction in AMPAR EPSCs. Both pep2m and LTD cause changes in quantal size and content without changes in AMPAR single-channel conductance or EPSC kinetics, suggesting an NSF-GluR2-dependent pool of AMPARs is specifically removed during LTD. Intracellular peptide infusion (pep2m); whole-cell patch clamp; LTD induction; minimal stimulation experiments in hippocampal slices Neuron High 10571232
2000 Trans-SNARE complexes (SNAREpins) assembled between opposing membranes are functionally resistant to disruption by NSF and alphaSNAP, becoming so at the moment of formation; this resistance allows fusion to proceed despite NSF activity in the surrounding environment that normally dismantles cis-SNARE complexes. Reconstituted liposome fusion assay with isolated SNARE proteins; NSF/alphaSNAP addition to trans- vs cis-SNARE complexes The Journal of cell biology High 10831610
2001 In Saccharomyces cerevisiae, Sec18p (NSF) and SNAREs (including Vti1p) are required for fusion of autophagosomes with the vacuole but are not involved in autophagosome formation itself. Temperature-shift experiments with sec18 yeast mutant; monitoring of autophagy flux and vacuolar delivery Molecular biology of the cell Medium 11694599
2001 NSF ATPase activity and alpha-/beta-SNAPs disassemble the AMPA receptor GluR2-PICK1 complex. GluR2, PICK1, NSF, and alpha-/beta-SNAPs form a complex in the presence of ATPgammaS; NSF ATPase disrupts PICK1-GluR2 interactions. Alpha- and beta-SNAP have differential effects, and SNAP overexpression in hippocampal neurons alters AMPAR trafficking by acting on GluR2-PICK1 complexes. This is the first non-SNARE substrate identified for NSF disassembly activity. In vitro complex assembly with ATPgammaS; ATPase-dependent disassembly assay; SNAP overexpression in cultured neurons with AMPAR trafficking readout Neuron High 11931741
2001 Ergosterol is required for the Sec18p (NSF)-mediated priming step of homotypic vacuole fusion. Ergosterol ligands (filipin, nystatin, amphotericin B) block in vitro vacuole fusion specifically at the priming stage, inhibiting Sec17p release from vacuoles, and their action is prevented by a reversible delay in Sec18p action. In vitro vacuole fusion assay; lipid manipulation with ergosterol ligands; genetic deletion of ERG genes; reversible inhibition kinetics The EMBO journal High 11483507
2001 The ionic layer of the SNARE complex (specifically, the glutamine residue of syntaxin) is required for efficient alpha-SNAP/NSF-mediated disassembly. Mutation of this glutamine allows SNARE complex binding to alpha-SNAP and NSF and ATP hydrolysis but prevents dissociation into SNARE monomers, indicating the ionic layer couples ATP hydrolysis to complex dissociation. SNARE complex mutagenesis; in vitro NSF disassembly assay with ATPgammaS/ATP; gel-shift analysis Proceedings of the National Academy of Sciences of the United States of America High 11762430
2001 SNARE complex disassembly by NSF follows (rather than precedes) synaptic vesicle fusion in Drosophila. Genetic interaction studies show that blocking evoked fusion delays accumulation of assembled SNARE complexes in comatose mutants. Double comatose/shibire mutants can deplete the entire vesicle pool, demonstrating NSF activity is not required for the fusion step itself. Drosophila genetic epistasis (comatose × para and comatose × shibire double mutants); behavioral paralysis assay; biochemical SNARE complex accumulation Proceedings of the National Academy of Sciences of the United States of America High 11593041
2002 AP2 (clathrin adaptor) associates with GluR2 at a region overlapping the NSF binding site. Dissecting NSF vs AP2 binding with specific GluR2 mutants shows AP2 mediates NMDA-induced (but not ligand-dependent) AMPA receptor internalization and is essential for LTD, while NSF maintains synaptic AMPAR responses but is not required for NMDA receptor-mediated internalization or LTD. GluR2 mutant constructs dissociating NSF vs AP2 binding; co-immunoprecipitation; receptor internalization assays; hippocampal LTD recordings Neuron High 12441055
2002 Ablation of NSF binding to GluR2 results in increased AMPA receptor endocytosis in response to AMPA or NMDA compared to wild-type, while loss of GRIP/ABP binding stabilizes an intracellular pool of internalized AMPARs and inhibits recycling, defining distinct roles for NSF (preventing excess endocytosis) vs GRIP/ABP (preventing recycling from intracellular stores). Epitope-tagged GluR2 mutants lacking NSF or PDZ binding; surface expression assays; endocytosis measurements in neurons Proceedings of the National Academy of Sciences of the United States of America Medium 12011465
2002 NSF has an ATPase-independent function distinct from SNARE disassembly that is essential for Golgi membrane fusion. The Golgi-reassembly-defective mammalian NSF G274E mutant and Drosophila comatose NSF bind but cannot disassemble SNARE complexes and have almost no ATPase activity, yet retain activity in Golgi reassembly. NSF/alpha-SNAP catalyze binding of GATE-16 to GOS-28 (a Golgi v-SNARE) in an ATP-dependent but hydrolysis-independent manner, protecting the v-SNARE from binding its t-SNARE. Mammalian NSF mutant characterization; cell-free Golgi reassembly assay; SNARE disassembly assay; GATE-16/GOS-28 binding assay The Journal of cell biology High 12070132
2003 Dominant-interfering ATP hydrolysis-deficient NSF(E329Q) disrupts Golgi stack structure into dispersed vesicular elements and inhibits intra-Golgi transport (glycosaminoglycan sulfation), while dominant-interfering p97(E578Q) does not affect Golgi structure or function. This establishes that only NSF (not p97) is directly required for Golgi membrane fusion. Expression of ATP hydrolysis-deficient dominant-negative mutants NSF(E329Q) and p97(E578Q) in mammalian cells; Golgi morphology by immunofluorescence; glycosaminoglycan sulfation assay; VSV-G transport assay Molecular biology of the cell High 14617820
2005 NSF and PICK1 are specifically required for calcium-permeable AMPA receptor plasticity (CARP), the dynamic exchange of GluR2-lacking and GluR2-containing receptors at synapses. NSF, but not PICK1, is required for receptor stabilization at synapses; PICK1, but not NSF, regulates formation of extrasynaptic GluR2-containing receptor pools that are laterally mobilized into synapses during CARP. Dominant-negative NSF and PICK1 interference; GluR2 subunit tracking; electrophysiology; fluorescence imaging in hippocampal neurons Neuron Medium 15797551
2005 NSF interaction with the GluR2 C-terminal domain is necessary and sufficient for rapid direct synaptic insertion of AMPA receptors. Wild-type GluR2 inserts rapidly into plasma membrane from intracellular compartments and accumulates at synaptic sites; a GluR2 mutant defective in NSF binding (DeltaA849-Q853) or GluR3 (which does not interact with NSF) show slower kinetics and initial extrasynaptic insertion. Introducing the NSF-binding site into GluR3 confers GluR2-like kinetics and synaptic targeting. Cell-surface thrombin cleavage assay; GluR2 mutants and chimeras; live imaging of receptor surface delivery in hippocampal neurons Molecular and cellular neurosciences Medium 15797712
2005 There is a SEC18/NSF-independent protein sorting pathway from the yeast cortical ER to the plasma membrane, mediated by the C-terminal domain of Ist2p. This pathway operates independently of COPII vesicle formation and overrides other sorting signals. Temperature-sensitive sec18 yeast mutant; chimeric protein constructs; fluorescence microscopy of protein localization The Journal of cell biology Medium 15911878
2006 NSF interacts directly with the GABAB receptor (GBR) heterodimer, forming a ternary complex in rat brain synaptosomes and CHO cells regulated by agonist stimulation. NSF functions as a priming factor required for agonist-promoted GBR desensitization independently of receptor internalization: inhibition of NSF binding (via TAT-Pep-27) abolished desensitization and prevented both PKC recruitment and receptor phosphorylation. Co-immunoprecipitation from synaptosomes and CHO cells; TAT peptide inhibition; Ca2+ mobilization assay; hippocampal slice electrophysiology; PKC recruitment assay The EMBO journal Medium 16724110
2006 In zebrafish, nsf is required cell-autonomously in neurons for organization of nodes of Ranvier (sodium channel clustering) and myelin basic protein expression, independent of its role in synaptic vesicle fusion. Neural activity and chemical synapse function are not required for sodium channel clustering in the larval nervous system. Forward genetic screen in zebrafish; chimeric larval analysis (transplantation); pharmacological inhibition of neural activity and synaptic transmission; immunostaining Current biology High 16581508
2009 Alpha-SNAP contains a conserved membrane attachment site (an extended loop with two phenylalanine residues in the N-terminal domain) that facilitates NSF-driven disassembly of membrane-bound (but not soluble) SNARE complexes. Mutation of these phenylalanines prevents SNAPs from supporting disassembly of membrane-anchored SNARE complexes. In vitro SNARE disassembly assay comparing soluble vs membrane-bound substrates; site-directed mutagenesis of alpha-SNAP phenylalanines; liposome binding assay The Journal of biological chemistry High 19762473
2010 NSF-binding site within GluR2 intracellular domain is required for plasma membrane insertion of GluR2-containing AMPA receptors. RNA editing of the Q/R site in the ion channel region also plays a key role in GluR2 plasma membrane insertion. These two structural elements act in the same pathway for GluA2 and heteromeric GluA2/3 receptor delivery. pHluorin-tagged GluA2 with TIRF microscopy to visualize individual plasma membrane fusion events; GluA2 mutants lacking NSF binding or with Q/R editing changes Proceedings of the National Academy of Sciences of the United States of America High 20534470
2010 Polo-like kinase 2 (Plk2), an activity-inducible kinase, directly interacts with NSF through a specific motif (independent of canonical polo box sites), disrupts NSF-GluA2 interaction, promotes loss of surface GluA2, increases GluA2 association with PICK1 and GRIP1, and decreases synaptic AMPAR current. Plk2 engagement of NSF (not Plk2 kinase activity) is required for this homeostatic reduction in surface AMPAR. Co-immunoprecipitation; pulldown with Plk2 mutants; surface biotinylation; whole-cell patch clamp in hippocampal neurons; dominant-negative and deletion constructs Nature neuroscience High 20802490
2012 Cryo-EM structures of NSF hexamer in ATPgammaS, ADP-AlFx, and ADP states reveal parallel arrangement of D1 and D2 domains and nucleotide-dependent conformational changes. The 20S particle structure shows the SNARE complex held at two interaction interfaces around the C-terminus and N-terminal half of the SNARE complex. Single-particle cryo-EM and negative stain EM; 3D reconstruction of NSF hexamer and 20S particle Nature structural & molecular biology High 22307055
2013 NSF-mediated disassembly of all tested SNARE complexes is initiated by a conserved 1:1 interaction between alpha-SNAP and the ternary SNARE complex (not influenced by N-terminal SNARE domains). This 1:1 alpha-SNAP:SNARE complex is confirmed by multiangle light scattering; NSF binding follows. SNARE-stimulated ATP hydrolysis rate measurements; Michaelis-Menten kinetics; SNAP-SNARE binding constants; multiangle light scattering; four different SNARE complexes tested The Journal of biological chemistry High 23836889
2015 NSF disassembles a single SNARE complex in one round of ATP turnover using a 'spring-loaded' mechanism: upon ATP cleavage, the NSF hexamer develops internal tension with phosphate dissociation, then releases the tension in a burst within 20 ms resulting in SNARE disassembly and immediate release of SNARE proteins. Single-molecule fluorescence spectroscopy; magnetic tweezers; real-time monitoring of single SNARE complex disassembly Science High 25814585
2015 Sec17 (alpha-SNAP) can trigger fusion of trans-SNARE paired membranes without Sec18 (NSF) by binding to trans-SNARE complexes and inserting apolar loops into apposed membranes; Sec18 does not substitute for Sec17 in this fusion-triggering role. Sec17 thus has two functions: stimulating Sec18-mediated cis-SNARE disassembly and independently triggering trans-SNARE-dependent fusion. Proteoliposome fusion assay with SNARE proteins; Sec17 and Sec18 mutants (L291A/L292A, F21S/M22S) dissociating the two functions; liposome binding assays Proceedings of the National Academy of Sciences of the United States of America High 25902545
2016 LRRK2 phosphorylates NSF at threonine 645 in the ATP-binding pocket of the D2 domain. NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembly. Substitution of Thr645 with alanine abrogates LRRK2-mediated increased ATPase activity. In vitro kinase assay with LRRK2 and full-length NSF; phosphosite mapping; ATPase assay; SNARE complex disassembly assay; alanine substitution mutagenesis Molecular neurodegeneration High 26758690
2017 Sec17 (alpha-SNAP) and Sec18 (NSF) act twice in the vacuolar fusion cycle: first binding to trans-SNARE complexes to stimulate fusion (without requiring ATP hydrolysis), and then hydrolyzing ATP to disassemble cis-SNARE complexes. At physiological protein levels, Sec17 stimulates fusion through its central residues binding the 0-layer of the SNARE complex and its N-terminal apolar loop for membrane binding. Yeast vacuole fusion assay with Sec17 mutants; proteoliposome fusion with asymmetric SNARE arrangement; cis-SNARE disassembly assay; transmembrane-anchored Sec17 chimera eLife High 28718762
2018 Cryo-EM structure of the 20S supercomplex (NSF/2×alphaSNAP/neuronal SNARE complex) at ~3.9 Å reveals: two alphaSNAP molecules interface with a specific surface of the SNARE complex via electrostatic interactions; 15 N-terminal residues of SNAP-25A are loaded into the D1 ring pore of NSF via spiral interactions between a conserved NSF tyrosine residue and SNAP-25A backbone atoms, preceding ATP hydrolysis. Electron cryo-microscopy of 20S supercomplex; near-atomic resolution structure determination eLife High 30198481
2018 NSF disassembles ternary SNARE complexes in a single step within 100 ms; complexin-1 competes with alphaSNAP binding to the SNARE complex, reducing disassembly rate and increasing failed disassembly events, suggesting complexin differentially regulates cis vs trans SNARE complex disassembly. NSF also disassembles anti-parallel SNARE complexes, implicating it in quality control. Single-molecule FRET assay monitoring repeated rounds of NSF-mediated SNARE complex disassembly and reassembly; complexin-1 competition assay eLife High 29985126
2019 Formation of trans-SNARE complexes in the presence of NSF-alphaSNAP requires both Munc18-1 and Munc13-1, and is facilitated by synaptotagmin-1. Munc18-1, Munc13-1, complexin-1, and likely synaptotagmin-1 also contribute to maintaining assembled trans-SNARE complexes in the presence of NSF-alphaSNAP, preventing de-priming. Reconstituted proteoliposome system with defined protein components; SNARE complex formation assays with and without NSF-alphaSNAP; co-flotation and co-sedimentation assays eLife High 30657450

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 665 9267032
1990 SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast. Cell 459 2111733
1998 NSF binding to GluR2 regulates synaptic transmission. Neuron 452 9697854
1991 Compartmental organization of Golgi-specific protein modification and vacuolar protein sorting events defined in a yeast sec18 (NSF) mutant. The Journal of cell biology 377 2071670
2002 Clathrin adaptor AP2 and NSF interact with overlapping sites of GluR2 and play distinct roles in AMPA receptor trafficking and hippocampal LTD. Neuron 345 12441055
1995 An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments. Cell 317 7553851
1998 The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs. Neuron 306 9697855
1995 Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. The Journal of biological chemistry 300 7782301
2001 Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Molecular biology of the cell 299 11694599
1990 An abundant and ubiquitous homo-oligomeric ring-shaped ATPase particle related to the putative vesicle fusion proteins Sec18p and NSF. The EMBO journal 261 2140770
1999 Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. Neuron 254 10399941
1997 SNAREs and NSF in targeted membrane fusion. Current opinion in cell biology 249 9261050
1999 Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction. Neuron 241 10571232
1993 SNAP family of NSF attachment proteins includes a brain-specific isoform. Nature 240 8455721
2005 Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 212 15797551
1995 Different requirements for NSF, SNAP, and Rab proteins in apical and basolateral transport in MDCK cells. Cell 205 7758111
2001 The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors. Molecular and cellular neurosciences 190 11461150
1988 Characterization of a component of the yeast secretion machinery: identification of the SEC18 gene product. Molecular and cellular biology 188 3054509
2000 Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment. Journal of immunology (Baltimore, Md. : 1950) 177 10820264
1998 Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent. The Journal of cell biology 170 9456319
2002 NSF ATPase and alpha-/beta-SNAPs disassemble the AMPA receptor-PICK1 complex. Neuron 165 11931741
1993 Inactivation of YME1, a member of the ftsH-SEC18-PAS1-CDC48 family of putative ATPase-encoding genes, causes increased escape of DNA from mitochondria in Saccharomyces cerevisiae. Molecular and cellular biology 164 8355690
1996 Homotypic vacuole fusion requires Sec17p (yeast alpha-SNAP) and Sec18p (yeast NSF). The EMBO journal 157 8670830
2003 Distinct roles for the AAA ATPases NSF and p97 in the secretory pathway. Molecular biology of the cell 152 14617820
1997 Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis. The Journal of cell biology 147 9362506
1997 A novel Sec18p/NSF-dependent complex required for Golgi-to-endosome transport in yeast. Molecular biology of the cell 142 9201718
2004 A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP). The Journal of biological chemistry 139 15452121
2001 Ergosterol is required for the Sec18/ATP-dependent priming step of homotypic vacuole fusion. The EMBO journal 137 11483507
1995 Clostridial neurotoxins compromise the stability of a low energy SNARE complex mediating NSF activation of synaptic vesicle fusion. The EMBO journal 125 7588600
1999 Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. The Journal of biological chemistry 117 10196135
2016 LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate. Molecular neurodegeneration 108 26758690
2002 Differential roles for NSF and GRIP/ABP in AMPA receptor cycling. Proceedings of the National Academy of Sciences of the United States of America 108 12011465
2007 Cellular functions of NSF: not just SNAPs and SNAREs. FEBS letters 103 17397838
1998 NSF function in neurotransmitter release involves rearrangement of the SNARE complex downstream of synaptic vesicle docking. The Journal of neuroscience : the official journal of the Society for Neuroscience 102 9852562
2001 SNARE-complex disassembly by NSF follows synaptic-vesicle fusion. Proceedings of the National Academy of Sciences of the United States of America 101 11593041
2000 SNAREpins are functionally resistant to disruption by NSF and alphaSNAP. The Journal of cell biology 99 10831610
1994 The ATPase activity of N-ethylmaleimide-sensitive fusion protein (NSF) is regulated by soluble NSF attachment proteins. The Journal of biological chemistry 98 7961908
2001 N-ethylmaleimide sensitive factor (NSF) structure and function. International review of cytology 97 11352269
1995 A role for soluble NSF attachment proteins (SNAPs) in regulated exocytosis in adrenal chromaffin cells. The EMBO journal 97 7835334
1998 Analysis of regulated exocytosis in adrenal chromaffin cells: insights into NSF/SNAP/SNARE function. BioEssays : news and reviews in molecular, cellular and developmental biology 93 9619104
1995 Is NSF a fusion protein? Trends in cell biology 90 14732068
1998 Synaptic physiology and ultrastructure in comatose mutants define an in vivo role for NSF in neurotransmitter release. The Journal of neuroscience : the official journal of the Society for Neuroscience 88 9852561
1998 Regulation of neurotransmitter release kinetics by NSF. Science (New York, N.Y.) 86 9469810
2001 Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE (Q-soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein receptor) protein syntaxin 6. The Journal of biological chemistry 85 11384996
1999 Early requirement for alpha-SNAP and NSF in the secretory cascade in chromaffin cells. The EMBO journal 85 10369670
2015 Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover. Science (New York, N.Y.) 81 25814585
1998 A revised model for the oligomeric state of the N-ethylmaleimide-sensitive fusion protein, NSF. The Journal of biological chemistry 77 9624162
2018 Structural principles of SNARE complex recognition by the AAA+ protein NSF. eLife 75 30198481
1998 LMA1 binds to vacuoles at Sec18p (NSF), transfers upon ATP hydrolysis to a t-SNARE (Vam3p) complex, and is released during fusion. Cell 74 9657146
2016 Disease resistance through impairment of α-SNAP-NSF interaction and vesicular trafficking by soybean Rhg1. Proceedings of the National Academy of Sciences of the United States of America 73 27821740
2010 Plasma membrane insertion of the AMPA receptor GluA2 subunit is regulated by NSF binding and Q/R editing of the ion pore. Proceedings of the National Academy of Sciences of the United States of America 72 20534470
2008 N-ethylmaleimide-sensitive fusion protein (NSF) is involved in central sensitization in the spinal cord through GluR2 subunit composition switch after inflammation. The European journal of neuroscience 72 18598260
2002 Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion. The Journal of cell biology 70 12070132
2019 Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and αSNAP. eLife 67 30657450
2003 NSF and p97/VCP: similar at first, different at last. FEBS letters 67 14630332
1996 Characterization and subcellular localization of target membrane soluble NSF attachment protein receptors (t-SNAREs) in macrophages. Syntaxins 2, 3, and 4 are present on phagosomal membranes. Journal of immunology (Baltimore, Md. : 1950) 66 8666810
1994 Neurally expressed Drosophila genes encoding homologs of the NSF and SNAP secretory proteins. Proceedings of the National Academy of Sciences of the United States of America 62 8202553
1999 Cytosolic ATPases, p97 and NSF, are sufficient to mediate rapid membrane fusion. The EMBO journal 61 10205162
1997 A heterodimer of thioredoxin and I(B)2 cooperates with Sec18p (NSF) to promote yeast vacuole inheritance. The Journal of cell biology 61 9015301
2017 Characterization of the Soluble NSF Attachment Protein gene family identifies two members involved in additive resistance to a plant pathogen. Scientific reports 60 28338077
2010 Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation. Nature neuroscience 60 20802490
2008 Circulating fibrocytes: cellular basis for NSF. Journal of the American College of Radiology : JACR 60 18180007
2009 A conserved membrane attachment site in alpha-SNAP facilitates N-ethylmaleimide-sensitive factor (NSF)-driven SNARE complex disassembly. The Journal of biological chemistry 56 19762473
2004 alpha-SNAP and NSF are required in a priming step during the human sperm acrosome reaction. Molecular human reproduction 56 15542541
1996 Domains of alpha-SNAP required for the stimulation of exocytosis and for N-ethylmalemide-sensitive fusion protein (NSF) binding and activation. Molecular biology of the cell 55 8744944
2005 SEC18/NSF-independent, protein-sorting pathway from the yeast cortical ER to the plasma membrane. The Journal of cell biology 54 15911878
1999 An NSF function distinct from ATPase-dependent SNARE disassembly is essential for Golgi membrane fusion. Nature cell biology 54 10559959
2016 Review: Progresses in understanding N-ethylmaleimide sensitive factor (NSF) mediated disassembly of SNARE complexes. Biopolymers 51 27062050
2015 Sec17 can trigger fusion of trans-SNARE paired membranes without Sec18. Proceedings of the National Academy of Sciences of the United States of America 51 25902545
2011 Requirements for the catalytic cycle of the N-ethylmaleimide-Sensitive Factor (NSF). Biochimica et biophysica acta 51 21689688
1998 Soluble NSF-attachment proteins. The international journal of biochemistry & cell biology 51 9693958
1999 Constitutive calcium-independent release of Toxoplasma gondii dense granules occurs through the NSF/SNAP/SNARE/Rab machinery. The Journal of biological chemistry 50 9891012
2015 Recent Advances in Deciphering the Structure and Molecular Mechanism of the AAA+ ATPase N-Ethylmaleimide-Sensitive Factor (NSF). Journal of molecular biology 48 26546278
1995 Distinct roles for N-ethylmaleimide-sensitive fusion protein (NSF) suggested by the identification of a second Drosophila NSF homolog. The Journal of biological chemistry 48 7642522
2005 NSF/SNAPs and p97/p47/VCIP135 are sequentially required for cell cycle-dependent reformation of the ER network. Genes to cells : devoted to molecular & cellular mechanisms 46 16164599
2001 The ionic layer is required for efficient dissociation of the SNARE complex by alpha-SNAP and NSF. Proceedings of the National Academy of Sciences of the United States of America 46 11762430
1992 The activity of Golgi transport vesicles depends on the presence of the N-ethylmaleimide-sensitive factor (NSF) and a soluble NSF attachment protein (alpha SNAP) during vesicle formation. The Journal of cell biology 46 1522110
2017 Sec17/Sec18 act twice, enhancing membrane fusion and then disassembling cis-SNARE complexes. eLife 45 28718762
2012 Structural characterization of full-length NSF and 20S particles. Nature structural & molecular biology 45 22307055
2011 The Dsl1 protein tethering complex is a resident endoplasmic reticulum complex, which interacts with five soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptors (SNAREs): implications for fusion and fusion regulation. The Journal of biological chemistry 43 21550981
2006 Coordinated action of NSF and PKC regulates GABAB receptor signaling efficacy. The EMBO journal 43 16724110
1999 A critical role for N-ethylmaleimide-sensitive fusion protein (NSF) in platelet granule secretion. Blood 43 10438719
2008 Gadolinium-containing MRI contrast agents: important variations on a theme for NSF. Journal of the American College of Radiology : JACR 42 18180006
1994 The N-ethylmaleimide-sensitive fusion protein (NSF) is preferentially expressed in the nervous system. FEBS letters 42 8013662
1998 NSF--fusion and beyond. Trends in cell biology 41 9861668
1996 Association of the fusion protein NSF with clathrin-coated vesicle membranes. The EMBO journal 41 8631296
2006 nsf is essential for organization of myelinated axons in zebrafish. Current biology : CB 40 16581508
2018 NSF-mediated disassembly of on- and off-pathway SNARE complexes and inhibition by complexin. eLife 39 29985126
2008 NSF, Unc-18-1, dynamin-1 and HSP90 are inclusion body components in neuronal intranuclear inclusion disease identified by anti-SUMO-1-immunocapture. Acta neuropathologica 39 18836734
2013 Disassembly of all SNARE complexes by N-ethylmaleimide-sensitive factor (NSF) is initiated by a conserved 1:1 interaction between α-soluble NSF attachment protein (SNAP) and SNARE complex. The Journal of biological chemistry 37 23836889
2005 NSF interaction is important for direct insertion of GluR2 at synaptic sites. Molecular and cellular neurosciences 37 15797712
2002 Cell polarity and locomotion, as well as endocytosis, depend on NSF. Development (Cambridge, England) 37 12183371
1997 NSF is required for transport from early to late endosomes. Journal of cell science 37 9378758
1995 Reconstitution of vesiculated Golgi membranes into stacks of cisternae: requirement of NSF in stack formation. The Journal of cell biology 37 7730397
2011 Both pre- and postsynaptic activity of Nsf prevents degeneration of hair-cell synapses. PloS one 35 22073277
2014 NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species. Brain, behavior and evolution 34 24603302
1997 N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex. The Journal of biological chemistry 34 9325254
2002 NSF regulates membrane traffic along multiple pathways in Paramecium. Journal of cell science 33 12244131
2017 Roles of Cellular NSF Protein in Entry and Nuclear Egress of Budded Virions of Autographa californica Multiple Nucleopolyhedrovirus. Journal of virology 32 28747507
1991 Structure of Saccharomyces cerevisiae alg3, sec18 mutant oligosaccharides. The Journal of biological chemistry 32 2005096

Missed literature

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

No submissions yet.