n ethylmaleimide sensitive proteins


Summary: ATPases that are members of the AAA protein superfamily (ATPase family Associated with Diverse cellular Activities). The NSFs functions, acting in conjunction with SOLUBLE NSF ATTACHMENT PROTEINS (i.e. SNAPs, which have no relation to SNAP 25), are to dissociate SNARE complexes.

Top Publications

  1. Sollner T, Bennett M, Whiteheart S, Scheller R, Rothman J. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell. 1993;75:409-18 pubmed
    ..The alpha-SNAP-SNARE complex can bind NSF, and NSF-dependent hydrolysis of ATP dissociates the complex, separating syntaxin, SNAP-25, and VAMP. ATP hydrolysis by NSF may provide motion to initiate bilayer fusion. ..
  2. Joels G, Lamprecht R. Interaction between N-ethylmaleimide-sensitive factor and GluR2 is essential for fear memory formation in lateral amygdala. J Neurosci. 2010;30:15981-6 pubmed publisher
    ..These results show that GluR2-NSF interaction in LA is necessary for fear memory consolidation but not retrieval or persistence. ..
  3. Zarelli V, Ruete M, Roggero C, Mayorga L, Tomes C. PTP1B dephosphorylates N-ethylmaleimide-sensitive factor and elicits SNARE complex disassembly during human sperm exocytosis. J Biol Chem. 2009;284:10491-503 pubmed publisher
    ..Our findings demonstrate that phosphorylation of NSF on tyrosine residues prevents its SNARE complex dissociation activity and establish for the first time a role for PTP1B in the modulation of the membrane fusion machinery. ..
  4. Evers D, MATTA J, HOE H, Zarkowsky D, Lee S, Isaac J, et al. Plk2 attachment to NSF induces homeostatic removal of GluA2 during chronic overexcitation. Nat Neurosci. 2010;13:1199-207 pubmed publisher
    ..These data reveal that heightened synaptic activity, acting through Plk2, leads to homeostatic decreases in surface AMPAR expression via the direct dissociation of NSF from GluA2. ..
  5. Yang Y, Wang X, Zhou Q. Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spines modifications. Proc Natl Acad Sci U S A. 2010;107:11999-2004 pubmed publisher
    ..Thus, perisynaptic GluR2-lacking AMPARs play a critical role in controlling the reversibility of both synaptic and spine modifications. ..
  6. Happe S, Weidman P. Cell-free transport to distinct Golgi cisternae is compartment specific and ARF independent. J Cell Biol. 1998;140:511-23 pubmed
  7. Chou W, Wang D, McMahon T, Qi Z, Song M, Zhang C, et al. GABAA receptor trafficking is regulated by protein kinase C(epsilon) and the N-ethylmaleimide-sensitive factor. J Neurosci. 2010;30:13955-65 pubmed publisher
    ..Reducing NSF activity by inhibiting PKC? could help restore synaptic inhibition in disease states in which it is impaired. ..
  8. Holopainen J, Cheng C, Molday L, Johal G, Coleman J, Dyka F, et al. Interaction and localization of the retinitis pigmentosa protein RP2 and NSF in retinal photoreceptor cells. Biochemistry. 2010;49:7439-47 pubmed publisher
    ..Our studies indicate that RP2, in addition to serving as a regulator of Arl3, interacts with NSF, and this complex may play an important role in membrane protein trafficking in photoreceptors and other cells of the retina. ..
  9. Cabral M, Anjard C, Malhotra V, Loomis W, Kuspa A. Unconventional secretion of AcbA in Dictyostelium discoideum through a vesicular intermediate. Eukaryot Cell. 2010;9:1009-17 pubmed publisher
    ..We suggest that these AcbA-containing vesicles are secretion intermediates and that GRASP functions at a late step leading to the docking/fusion of these vesicles at the cell surface...

More Information


  1. Zhao C, Matveeva E, Ren Q, Whiteheart S. Dissecting the N-ethylmaleimide-sensitive factor: required elements of the N and D1 domains. J Biol Chem. 2010;285:761-72 pubmed publisher
    ..Taken together, these data establish functional roles for many of the structural elements of the N domain and of the D1 ATP-binding site of NSF. ..
  2. Yu W, Yu H, Chen Z, Strickland S. Disruption of laminin in the peripheral nervous system impedes nonmyelinating Schwann cell development and impairs nociceptive sensory function. Glia. 2009;57:850-9 pubmed publisher
    ..These results show that laminin participates in nonmyelinating SC development and Remak bundle formation and suggest a possible role for laminin deficiency in peripheral sensory neuropathies. ..
  3. Chen X, Ma X, Ma S, Coenraads P, Zhang C, Liu J, et al. Proteomic analysis of the rat ovary following chronic low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Toxicol Environ Health A. 2009;72:717-26 pubmed publisher
    ..Data provide further insight into the mechanisms by which TCDD disrupts ovarian function by indicating which differential protein expressions following low-dose TCDD exposure. ..
  4. Winter U, Chen X, Fasshauer D. A conserved membrane attachment site in alpha-SNAP facilitates N-ethylmaleimide-sensitive factor (NSF)-driven SNARE complex disassembly. J Biol Chem. 2009;284:31817-26 pubmed publisher
    ..This implies that the disassembly machinery is adapted to attack membrane-bound SNARE complexes, probably in their relaxed cis-configuration. ..
  5. Huang S, Brown B, Craft C. Visual Arrestin 1 acts as a modulator for N-ethylmaleimide-sensitive factor in the photoreceptor synapse. J Neurosci. 2010;30:9381-91 pubmed publisher
  6. Chen S, Liu F. Interaction of dopamine D1 receptor with N-ethylmaleimide-sensitive factor is important for the membrane localization of the receptor. J Neurosci Res. 2010;88:2504-12 pubmed publisher
    ..Our data indicate that the interaction between NSF and D1R is important for the membrane localization of D1R. ..
  7. Hammond J, McCullumsmith R, Funk A, Haroutunian V, Meador Woodruff J. Evidence for abnormal forward trafficking of AMPA receptors in frontal cortex of elderly patients with schizophrenia. Neuropsychopharmacology. 2010;35:2110-9 pubmed publisher
    ..Together, these data suggest that there is an alteration of forward trafficking of AMPA receptors as well as changes in the subcellular localization of an AMPA receptor subunit in schizophrenia. ..
  8. Mehrpour M, Esclatine A, Beau I, Codogno P. Overview of macroautophagy regulation in mammalian cells. Cell Res. 2010;20:748-62 pubmed publisher
  9. Araki Y, Lin D, Huganir R. Plasma membrane insertion of the AMPA receptor GluA2 subunit is regulated by NSF binding and Q/R editing of the ion pore. Proc Natl Acad Sci U S A. 2010;107:11080-5 pubmed publisher
    ..These results demonstrate that the plasma membrane delivery of GluA2 containing AMPA receptors is regulated by its unique structural elements. ..
  10. Goel A, Su B, Flavahan S, Lowenstein C, Berkowitz D, Flavahan N. Increased endothelial exocytosis and generation of endothelin-1 contributes to constriction of aged arteries. Circ Res. 2010;107:242-51 pubmed publisher
    ..Altered endothelial exocytosis of ET-1 and other mediators may contribute to cardiovascular pathology in aging. ..
  11. Kurrasch D, Nevin L, Wong J, Baier H, Ingraham H. Neuroendocrine transcriptional programs adapt dynamically to the supply and demand for neuropeptides as revealed in NSF mutant zebrafish. Neural Dev. 2009;4:22 pubmed publisher
    ..Based on our collective findings, we speculate that neuroendocrine transcriptional programs adapt dynamically to both the supply and demand for neuropeptides to ensure adequate homeostatic responses. ..
  12. Fukasawa M, Okamoto K, Nakamura M, Mikami K, Shimada S, Tanaka Y, et al. Proteomic analysis of the rat cerebellar flocculus during vestibular compensation. J Vestib Res. 2009;19:83-94 pubmed publisher
    ..Our results enhance the understanding of the role of the cerebellar flocculi in VC generation. ..
  13. Arasaki K, Roy C. Legionella pneumophila promotes functional interactions between plasma membrane syntaxins and Sec22b. Traffic. 2010;11:587-600 pubmed publisher
    ..pneumophila promotes pairing of plasma membrane syntaxins and Sec22b could provide unique insight into how the secretory vesicles could provide an additional membrane reserve subverted during phagosome maturation. ..
  14. Lamprecht R, Dracheva S, Assoun S, Ledoux J. Fear conditioning induces distinct patterns of gene expression in lateral amygdala. Genes Brain Behav. 2009;8:735-43 pubmed publisher
    ..These results show that fear conditioning induces a unique temporal activation of molecular pathways involved in regulating synaptic transmission and axonal morphology in LA, which is different from non-associative stimulation. ..
  15. Kawasaki F, Ordway R. Molecular mechanisms determining conserved properties of short-term synaptic depression revealed in NSF and SNAP-25 conditional mutants. Proc Natl Acad Sci U S A. 2009;106:14658-63 pubmed publisher
    ..Together, the results reported here establish in vivo contributions of SNAP-25 and NSF to synaptic vesicle trafficking and define molecular mechanisms determining conserved functional properties of short-term depression. ..
  16. Thielmann Y, Weiergräber O, Ma P, Schwarten M, Mohrlüder J, Willbold D. Comparative modeling of human NSF reveals a possible binding mode of GABARAP and GATE-16. Proteins. 2009;77:637-46 pubmed publisher
    ..Furthermore, we propose a binding site for the ubiquitin-like proteins GABARAP and GATE-16, which is supported by experimental evidence, yielding a complex with favorable surface complementarity. ..
  17. Zhao C, Hellman L, Zhan X, Bowman W, Whiteheart S, Fried M. Hexahistidine-tag-specific optical probes for analyses of proteins and their interactions. Anal Biochem. 2010;399:237-45 pubmed publisher
    ..In addition, fluorescence resonance energy transfer (FRET) between (Ni(2+)-NTA)(2)-Cy3-labeled proteins and suitable donors/acceptors provides a convenient assay for binding interactions and for measurements of donor-acceptor distances. ..
  18. Fader C, Sánchez D, Mestre M, Colombo M. TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim Biophys Acta. 2009;1793:1901-16 pubmed publisher
    ..Furthermore, VAMP7 and ATPase NSF, a protein required for SNAREs disassembly, participate in the fusion between MVBs with the plasma membrane to release the internal vesicles (i.e., exosomes) into the extracellular medium. ..
  19. Patten S, Ali D. PKCgamma-induced trafficking of AMPA receptors in embryonic zebrafish depends on NSF and PICK1. Proc Natl Acad Sci U S A. 2009;106:6796-801 pubmed publisher
    ..The present data further our understanding of AMPAR trafficking, and have important implications for synaptic development and synaptic plasticity. ..
  20. Littleton J, Barnard R, Titus S, Slind J, Chapman E, Ganetzky B. SNARE-complex disassembly by NSF follows synaptic-vesicle fusion. Proc Natl Acad Sci U S A. 2001;98:12233-8 pubmed
    ..In the absence of NSF activity, there are sufficient fusion-competent SNAREs to exocytose both the readily released and the reserve pool of synaptic vesicles. ..