N-ethylmaleimide sensitive fusion protein: Difference between revisions

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{{PBB_Controls<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{DISPLAYTITLE:''N''-ethylmaleimide sensitive fusion protein}}
| update_page = yes
{{Infobox_gene}}
| require_manual_inspection = no
'''''N''-ethylmaleimide-sensitive factor''', also known as '''NSF''' or '''''N''-ethylmaleimide sensitive fusion proteins''', is an [[enzyme]] which in humans is encoded by the ''NSF'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NSF N-ethylmaleimide-sensitive factor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4905}}</ref><ref name="pmid1315316">{{cite journal | vauthors = Wilson DW, Whiteheart SW, Wiedmann M, Brunner M, Rothman JE | title = A multisubunit particle implicated in membrane fusion | journal = The Journal of Cell Biology | volume = 117 | issue = 3 | pages = 531–8 | date = May 1992 | pmid = 1315316 | pmc = 2289450 | doi = 10.1083/jcb.117.3.531 }}</ref><ref name="pmid8875895">{{cite journal | vauthors = Hoyle J, Phelan JP, Bermingham N, Fisher EM | title = Localization of human and mouse N-ethylmaleimide-sensitive factor (NSF) gene: a two-domain member of the AAA family that is involved in membrane fusion | journal = Mammalian Genome | volume = 7 | issue = 11 | pages = 850–2 | date = Nov 1996 | pmid = 8875895 | doi = 10.1007/s003359900249 }}</ref>
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}
{{GNF_Protein_box<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
| image = PBB_Protein_NSF_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1d2n.
| PDB = {{PDB2|1d2n}}, {{PDB2|1nsf}}, {{PDB2|1qcs}}, {{PDB2|1qdn}}
| Name = N-ethylmaleimide-sensitive factor
| HGNCid = 8016
| Symbol = NSF
| AltSymbols =; SKD2
| OMIM = 601633
| ECnumber = 
| Homologene = 4502
| MGIid = 104560
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0017111 |text = nucleoside-triphosphatase activity}} {{GNF_GO|id=GO:0019905 |text = syntaxin binding}} {{GNF_GO|id=GO:0042623 |text = ATPase activity, coupled}}
| Component = {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}}
| Process = {{GNF_GO|id=GO:0015031 |text = protein transport}}  
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4905
    | Hs_Ensembl = 
    | Hs_RefseqProtein = XP_001128468
    | Hs_RefseqmRNA = XM_001128468
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 18195
    | Mm_Ensembl = ENSMUSG00000034187
    | Mm_RefseqmRNA = NM_008740
    | Mm_RefseqProtein = NP_032766
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 103637872
    | Mm_GenLoc_end = 103770146
    | Mm_Uniprot = Q8BQ65
  }}
}}
'''N-ethylmaleimide-sensitive factor''', also known as '''NSF''' or '''N-ethylmaleimide sensitive fusion proteins''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NSF N-ethylmaleimide-sensitive factor| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4905| accessdate = }}</ref> It is a trimeric ATPase involved in membrane fusion.
NSF is ubiquitously found in the [[cytoplasm]] of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane [[vesicle (biology) |vesicles]] from one membrane compartment to another. During this process, [[SNARE]] proteins on two joining membranes (usually a vesicle and a target membrane such as the [[plasma membrane]]) form a tight complex. This aids fusion of the vesicle with the target membrane. The role of NSF is to undo these SNARE complexes once membrane fusion has occurred, using the hydrolysis of [[Adenosine triphosphate | ATP]] as an energy source. The dissociated SNAREs can then be recycled for reuse in further rounds of membrane fusion.


==SNARE hypothesis==
== Function ==


Because  neuronal function depends on the release of [[neurotransmitter]]s at a [[synapse]] — a process in which [[synaptic vesicle]]s fuse with the presynaptic membrane — NSF is a key synaptic component. Thus, conditional temperature-sensitive [[mutation]]s in the [[Drosophila]] gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked. In [[Dictyostelium]] amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration. Another neuronal role for NSF is indicated by its direct binding to the GluR2 subunit of [[AMPA receptor|AMPA]] type [[glutamate receptor|glutamate receptors]] (which detect the neurotransmitter [[glutamate]]). This gives NSF a putative role in delivery and [[gene expression|expression]] of AMPA receptors at the [[synapse]]<ref>Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL and Henley JM, 1999. Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism. ''Neuron'', '''23'''(2):365-76.</ref>.
NSF is a homohexameric [[AAA proteins|AAA]] [[ATPase]] involved in membrane fusion.<ref name="pmid12941689">{{cite journal | vauthors = Furst J, Sutton RB, Chen J, Brunger AT, Grigorieff N | title = Electron cryomicroscopy structure of N-ethyl maleimide sensitive factor at 11 A resolution | journal = The EMBO Journal | volume = 22 | issue = 17 | pages = 4365–74 | date = Sep 2003 | pmid = 12941689 | pmc = 202363 | doi = 10.1093/emboj/cdg420 }}</ref> NSF is ubiquitously found in the [[cytoplasm]] of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane [[vesicle (biology)|vesicles]] from one membrane compartment to another. During this process, [[SNARE]] proteins on two joining membranes (usually a vesicle and a target membrane such as the [[plasma membrane]]) form a tight complex. This aids fusion of the vesicle with the target membrane. It has been proposed that the role of NSF is to undo these SNARE complexes once membrane fusion has occurred, using the hydrolysis of [[Adenosine triphosphate|ATP]] as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion.<ref name="Alberts 2008">{{cite book | last = Alberts | first = Bruce | title = Molecular biology of the cell | publisher = [[Garland Science]] | year = 2008 | isbn = 978-0-8153-4105-5 }}</ref>  This proposal remains controversial, however. Recent work indicates that the ATPase function of NSF does not function in recycling of vesicles but rather functions in the act of fusing vesicles with the plasma membrane.<ref name="pmid18172208">{{cite journal | vauthors = Kuner T, Li Y, Gee KR, Bonewald LF, Augustine GJ | title = Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 1 | pages = 347–52 | date = Jan 2008 | pmid = 18172208 | pmc = 2224215 | doi = 10.1073/pnas.0707197105 | url = http://www.pnas.org/content/105/1/347.long }}</ref>


NSF was discovered by [[James Rothman]] and colleagues in 1979 whilst at [[Stanford University]]; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with [[N-ethylmaleimide]]. This assay enabled them to purify NSF.
== SNARE hypothesis ==


==References==
Because  neuronal function depends on the release of [[neurotransmitter]]s at a [[synapse]] — a process in which [[synaptic vesicle]]s fuse with the presynaptic membrane — NSF is a key synaptic component. Thus, conditional temperature-sensitive [[mutation]]s in the ''[[Drosophila melanogaster]]'' gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked. In ''[[Dictyostelium discoideum]]'' amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration. Another neuronal role for NSF is indicated by its direct binding to the GluR2 subunit of [[AMPA receptor|AMPA]] type [[glutamate receptor]]s (which detect the neurotransmitter [[glutamate]]). This gives NSF a putative role in delivery and [[gene expression|expression]] of AMPA receptors at the [[synapse]].<ref name="pmid10399941">{{cite journal | vauthors = Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL, Henley JM | title = Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism | journal = Neuron | volume = 23 | issue = 2 | pages = 365–76 | date = Jun 1999 | pmid = 10399941 | doi = 10.1016/S0896-6273(00)80786-2 }}</ref>
{{reflist|2}}
 
==Further reading==
NSF was discovered by [[James Rothman]] and colleagues in 1987 while at [[Stanford University]]; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with [[N-ethylmaleimide|''N''-ethylmaleimide]]. This assay enabled them to purify NSF.<ref name="pmid3821906">{{cite journal | vauthors = Glick BS, Rothman JE | title = Possible role for fatty acyl-coenzyme A in intracellular protein transport | journal = Nature | volume = 326 | issue = 6110 | pages = 309–12 | year = 1987 | pmid = 3821906 | doi = 10.1038/326309a0 }}</ref>
 
== Interactions ==
 
''N''-ethylmaleimide sensitive fusion protein has been shown to [[Protein-protein interaction|interact]] with [[NAPA (gene)|NAPA]].<ref name=pmid9362506>{{cite journal | vauthors = Barnard RJ, Morgan A, Burgoyne RD | title = Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis | journal = The Journal of Cell Biology | volume = 139 | issue = 4 | pages = 875–83 | date = Nov 1997 | pmid = 9362506 | pmc = 2139964 | doi = 10.1083/jcb.139.4.875 }}</ref><ref name=pmid7622514>{{cite journal | vauthors = Hanson PI, Otto H, Barton N, Jahn R | title = The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin | journal = The Journal of Biological Chemistry | volume = 270 | issue = 28 | pages = 16955–61 | date = Jul 1995 | pmid = 7622514 | doi = 10.1074/jbc.270.28.16955 }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Wilson DW, Whiteheart SW, Wiedmann M, Brunner M, Rothman JE | title = A multisubunit particle implicated in membrane fusion | journal = The Journal of Cell Biology | volume = 117 | issue = 3 | pages = 531–8 | date = May 1992 | pmid = 1315316 | pmc = 2289450 | doi = 10.1083/jcb.117.3.531 }}
| citations =
* {{cite journal | vauthors = Hanson PI, Otto H, Barton N, Jahn R | title = The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin | journal = The Journal of Biological Chemistry | volume = 270 | issue = 28 | pages = 16955–61 | date = Jul 1995 | pmid = 7622514 | doi = 10.1074/jbc.270.28.16955 }}
*{{cite journal | author=Wilson DW, Whiteheart SW, Wiedmann M, ''et al.'' |title=A multisubunit particle implicated in membrane fusion. |journal=J. Cell Biol. |volume=117 |issue= 3 |pages= 531-8 |year= 1992 |pmid= 1315316 |doi=   | doi=10.1083/jcb.117.3.531}}
* {{cite journal | vauthors = Püschel AW, O'Connor V, Betz H | title = The N-ethylmaleimide-sensitive fusion protein (NSF) is preferentially expressed in the nervous system | journal = FEBS Letters | volume = 347 | issue = 1 | pages = 55–8 | date = Jun 1994 | pmid = 8013662 | doi = 10.1016/0014-5793(94)00505-2 }}
*{{cite journal | author=Hanson PI, Otto H, Barton N, Jahn R |title=The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin. |journal=J. Biol. Chem. |volume=270 |issue= 28 |pages= 16955-61 |year= 1995 |pmid= 7622514 |doi= }}
* {{cite journal | vauthors = Whiteheart SW, Rossnagel K, Buhrow SA, Brunner M, Jaenicke R, Rothman JE | title = N-ethylmaleimide-sensitive fusion protein: a trimeric ATPase whose hydrolysis of ATP is required for membrane fusion | journal = The Journal of Cell Biology | volume = 126 | issue = 4 | pages = 945–54 | date = Aug 1994 | pmid = 8051214 | pmc = 2120109 | doi = 10.1083/jcb.126.4.945 }}
*{{cite journal | author=Püschel AW, O'Connor V, Betz H |title=The N-ethylmaleimide-sensitive fusion protein (NSF) is preferentially expressed in the nervous system. |journal=FEBS Lett. |volume=347 |issue= 1 |pages= 55-8 |year= 1994 |pmid= 8013662 |doi=    | doi=10.1016/0014-5793(94)00505-2}}
* {{cite journal | vauthors = Nagahama M, Orci L, Ravazzola M, Amherdt M, Lacomis L, Tempst P, Rothman JE, Söllner TH | title = A v-SNARE implicated in intra-Golgi transport | journal = The Journal of Cell Biology | volume = 133 | issue = 3 | pages = 507–16 | date = May 1996 | pmid = 8636227 | pmc = 2120813 | doi = 10.1083/jcb.133.3.507 }}
*{{cite journal | author=Whiteheart SW, Rossnagel K, Buhrow SA, ''et al.'' |title=N-ethylmaleimide-sensitive fusion protein: a trimeric ATPase whose hydrolysis of ATP is required for membrane fusion. |journal=J. Cell Biol. |volume=126 |issue= 4 |pages= 945-54 |year= 1994 |pmid= 8051214 |doi=   | doi=10.1083/jcb.126.4.945}}
* {{cite journal | vauthors = Hoyle J, Phelan JP, Bermingham N, Fisher EM | title = Localization of human and mouse N-ethylmaleimide-sensitive factor (NSF) gene: a two-domain member of the AAA family that is involved in membrane fusion | journal = Mammalian Genome | volume = 7 | issue = 11 | pages = 850–2 | date = Nov 1996 | pmid = 8875895 | doi = 10.1007/s003359900249 }}
*{{cite journal | author=Nagahama M, Orci L, Ravazzola M, ''et al.'' |title=A v-SNARE implicated in intra-Golgi transport. |journal=J. Cell Biol. |volume=133 |issue= 3 |pages= 507-16 |year= 1996 |pmid= 8636227 |doi=   | doi=10.1083/jcb.133.3.507}}
* {{cite journal | vauthors = Jacobsson G, Meister B | title = Molecular components of the exocytotic machinery in the rat pituitary gland | journal = Endocrinology | volume = 137 | issue = 12 | pages = 5344–56 | date = Dec 1996 | pmid = 8940356 | doi = 10.1210/en.137.12.5344 }}
*{{cite journal | author=Hoyle J, Phelan JP, Bermingham N, Fisher EM |title=Localization of human and mouse N-ethylmaleimide-sensitive factor (NSF) gene: a two-domain member of the AAA family that is involved in membrane fusion. |journal=Mamm. Genome |volume=7 |issue= 11 |pages= 850-2 |year= 1997 |pmid= 8875895 |doi= }}
* {{cite journal | vauthors = Timmers KI, Clark AE, Omatsu-Kanbe M, Whiteheart SW, Bennett MK, Holman GD, Cushman SW | title = Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein | journal = The Biochemical Journal | volume = 320 | issue = 2 | pages = 429–36 | date = Dec 1996 | pmid = 8973549 | pmc = 1217948 | doi =  10.1042/bj3200429}}
*{{cite journal | author=Jacobsson G, Meister B |title=Molecular components of the exocytotic machinery in the rat pituitary gland. |journal=Endocrinology |volume=137 |issue= 12 |pages= 5344-56 |year= 1997 |pmid= 8940356 |doi= }}
* {{cite journal | vauthors = Germain-Lee EL, Obie C, Valle D | title = NVL: a new member of the AAA family of ATPases localized to the nucleus | journal = Genomics | volume = 44 | issue = 1 | pages = 22–34 | date = Aug 1997 | pmid = 9286697 | doi = 10.1006/geno.1997.4856 }}
*{{cite journal | author=Timmers KI, Clark AE, Omatsu-Kanbe M, ''et al.'' |title=Identification of SNAP receptors in rat adipose cell membrane fractions and in SNARE complexes co-immunoprecipitated with epitope-tagged N-ethylmaleimide-sensitive fusion protein. |journal=Biochem. J. |volume=320 ( Pt 2) |issue= |pages= 429-36 |year= 1997 |pmid= 8973549 |doi=  }}
* {{cite journal | vauthors = Subramaniam VN, Loh E, Hong W | title = N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex | journal = The Journal of Biological Chemistry | volume = 272 | issue = 41 | pages = 25441–4 | date = Oct 1997 | pmid = 9325254 | doi = 10.1074/jbc.272.41.25441 }}
*{{cite journal | author=Germain-Lee EL, Obie C, Valle D |title=NVL: a new member of the AAA family of ATPases localized to the nucleus. |journal=Genomics |volume=44 |issue= 1 |pages= 22-34 |year= 1997 |pmid= 9286697 |doi= 10.1006/geno.1997.4856 }}
* {{cite journal | vauthors = Lowe SL, Peter F, Subramaniam VN, Wong SH, Hong W | title = A SNARE involved in protein transport through the Golgi apparatus | journal = Nature | volume = 389 | issue = 6653 | pages = 881–4 | date = Oct 1997 | pmid = 9349823 | doi = 10.1038/39923 }}
*{{cite journal | author=Subramaniam VN, Loh E, Hong W |title=N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex. |journal=J. Biol. Chem. |volume=272 |issue= 41 |pages= 25441-4 |year= 1997 |pmid= 9325254 |doi=   | doi=10.1074/jbc.272.41.25441}}
* {{cite journal | vauthors = Barnard RJ, Morgan A, Burgoyne RD | title = Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis | journal = The Journal of Cell Biology | volume = 139 | issue = 4 | pages = 875–83 | date = Nov 1997 | pmid = 9362506 | pmc = 2139964 | doi = 10.1083/jcb.139.4.875 }}
*{{cite journal | author=Lowe SL, Peter F, Subramaniam VN, ''et al.'' |title=A SNARE involved in protein transport through the Golgi apparatus. |journal=Nature |volume=389 |issue= 6653 |pages= 881-4 |year= 1997 |pmid= 9349823 |doi= 10.1038/39923 }}
* {{cite journal | vauthors = Osten P, Srivastava S, Inman GJ, Vilim FS, Khatri L, Lee LM, States BA, Einheber S, Milner TA, Hanson PI, Ziff EB | title = The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs | journal = Neuron | volume = 21 | issue = 1 | pages = 99–110 | date = Jul 1998 | pmid = 9697855 | doi = 10.1016/S0896-6273(00)80518-8 }}
*{{cite journal | author=Barnard RJ, Morgan A, Burgoyne RD |title=Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis. |journal=J. Cell Biol. |volume=139 |issue= 4 |pages= 875-83 |year= 1997 |pmid= 9362506 |doi=   | doi=10.1083/jcb.139.4.875}}
* {{cite journal | vauthors = McDonald PH, Cote NL, Lin FT, Premont RT, Pitcher JA, Lefkowitz RJ | title = Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation | journal = The Journal of Biological Chemistry | volume = 274 | issue = 16 | pages = 10677–80 | date = Apr 1999 | pmid = 10196135 | doi = 10.1074/jbc.274.16.10677 }}
*{{cite journal | author=Osten P, Srivastava S, Inman GJ, ''et al.'' |title=The AMPA receptor GluR2 C terminus can mediate a reversible, ATP-dependent interaction with NSF and alpha- and beta-SNAPs. |journal=Neuron |volume=21 |issue= 1 |pages= 99-110 |year= 1998 |pmid= 9697855 |doi=    | doi=10.1016/S0896-6273(00)80518-8}}
* {{cite journal | vauthors = Subramaniam VN, Loh E, Horstmann H, Habermann A, Xu Y, Coe J, Griffiths G, Hong W | title = Preferential association of syntaxin 8 with the early endosome | journal = Journal of Cell Science | volume = 113 | issue = 6 | pages = 997–1008 | date = Mar 2000 | pmid = 10683148 | doi =  }}
*{{cite journal | author=McDonald PH, Cote NL, Lin FT, ''et al.'' |title=Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2-adrenergic receptor regulation. |journal=J. Biol. Chem. |volume=274 |issue= 16 |pages= 10677-80 |year= 1999 |pmid= 10196135 |doi=    | doi=10.1074/jbc.274.16.10677}}
* {{cite journal | vauthors = Sagiv Y, Legesse-Miller A, Porat A, Elazar Z | title = GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28 | journal = The EMBO Journal | volume = 19 | issue = 7 | pages = 1494–504 | date = Apr 2000 | pmid = 10747018 | pmc = 310219 | doi = 10.1093/emboj/19.7.1494 }}
*{{cite journal | author=Subramaniam VN, Loh E, Horstmann H, ''et al.'' |title=Preferential association of syntaxin 8 with the early endosome. |journal=J. Cell. Sci. |volume=113 ( Pt 6) |issue= |pages= 997-1008 |year= 2000 |pmid= 10683148 |doi=  }}
* {{cite journal | vauthors = Allan BB, Moyer BD, Balch WE | title = Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion | journal = Science | volume = 289 | issue = 5478 | pages = 444–8 | date = Jul 2000 | pmid = 10903204 | doi = 10.1126/science.289.5478.444 }}
*{{cite journal | author=Sagiv Y, Legesse-Miller A, Porat A, Elazar Z |title=GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. |journal=EMBO J. |volume=19 |issue= 7 |pages= 1494-504 |year= 2000 |pmid= 10747018 |doi= 10.1093/emboj/19.7.1494 }}
* {{cite journal | vauthors = Michaut M, Tomes CN, De Blas G, Yunes R, Mayorga LS | title = Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 18 | pages = 9996–10001 | date = Aug 2000 | pmid = 10954749 | pmc = 27650 | doi = 10.1073/pnas.180206197 }}
*{{cite journal | author=Allan BB, Moyer BD, Balch WE |title=Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. |journal=Science |volume=289 |issue= 5478 |pages= 444-8 |year= 2000 |pmid= 10903204 |doi=    | doi=10.1126/science.289.5478.444}}
* {{cite journal | vauthors = Imai C, Sugai T, Iritani S, Niizato K, Nakamura R, Makifuchi T, Kakita A, Takahashi H, Nawa H | title = A quantitative study on the expression of synapsin II and N-ethylmaleimide-sensitive fusion protein in schizophrenic patients | journal = Neuroscience Letters | volume = 305 | issue = 3 | pages = 185–8 | date = Jun 2001 | pmid = 11403936 | doi = 10.1016/S0304-3940(01)01844-4 }}
*{{cite journal | author=Michaut M, Tomes CN, De Blas G, ''et al.'' |title=Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 18 |pages= 9996-10001 |year= 2000 |pmid= 10954749 |doi= 10.1073/pnas.180206197 }}
* {{cite journal | vauthors = Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ | title = 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 | journal = Molecular and Cellular Neurosciences | volume = 18 | issue = 1 | pages = 13–25 | date = Jul 2001 | pmid = 11461150 | doi = 10.1006/mcne.2001.1005 }}
*{{cite journal | author=Imai C, Sugai T, Iritani S, ''et al.'' |title=A quantitative study on the expression of synapsin II and N-ethylmaleimide-sensitive fusion protein in schizophrenic patients. |journal=Neurosci. Lett. |volume=305 |issue= 3 |pages= 185-8 |year= 2001 |pmid= 11403936 |doi=    | doi=10.1016/S0304-3940(01)01844-4}}
*{{cite journal | author=Kittler JT, Rostaing P, Schiavo G, ''et al.'' |title=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. |journal=Mol. Cell. Neurosci. |volume=18 |issue= 1 |pages= 13-25 |year= 2001 |pmid= 11461150 |doi= 10.1006/mcne.2001.1005 }}
}}
{{refend}}
{{refend}}


{{PDB Gallery|geneid=4905}}
{{DEFAULTSORT:N-Ethylmaleimide Sensitive Fusion Protein}}
[[Category:Proteins]]
[[Category:Proteins]]
{{protein-stub}}
[[Category:Human proteins]]
{{WikiDoc Sources}}

Latest revision as of 12:19, 5 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Wikidata
View/Edit Human

N-ethylmaleimide-sensitive factor, also known as NSF or N-ethylmaleimide sensitive fusion proteins, is an enzyme which in humans is encoded by the NSF gene.[1][2][3]

Function

NSF is a homohexameric AAA ATPase involved in membrane fusion.[4] NSF is ubiquitously found in the cytoplasm of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane vesicles from one membrane compartment to another. During this process, SNARE proteins on two joining membranes (usually a vesicle and a target membrane such as the plasma membrane) form a tight complex. This aids fusion of the vesicle with the target membrane. It has been proposed that the role of NSF is to undo these SNARE complexes once membrane fusion has occurred, using the hydrolysis of ATP as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion.[5] This proposal remains controversial, however. Recent work indicates that the ATPase function of NSF does not function in recycling of vesicles but rather functions in the act of fusing vesicles with the plasma membrane.[6]

SNARE hypothesis

Because neuronal function depends on the release of neurotransmitters at a synapse — a process in which synaptic vesicles fuse with the presynaptic membrane — NSF is a key synaptic component. Thus, conditional temperature-sensitive mutations in the Drosophila melanogaster gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked. In Dictyostelium discoideum amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration. Another neuronal role for NSF is indicated by its direct binding to the GluR2 subunit of AMPA type glutamate receptors (which detect the neurotransmitter glutamate). This gives NSF a putative role in delivery and expression of AMPA receptors at the synapse.[7]

NSF was discovered by James Rothman and colleagues in 1987 while at Stanford University; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with N-ethylmaleimide. This assay enabled them to purify NSF.[8]

Interactions

N-ethylmaleimide sensitive fusion protein has been shown to interact with NAPA.[9][10]

References

  1. ↑ "Entrez Gene: NSF N-ethylmaleimide-sensitive factor".
  2. ↑ Wilson DW, Whiteheart SW, Wiedmann M, Brunner M, Rothman JE (May 1992). "A multisubunit particle implicated in membrane fusion". The Journal of Cell Biology. 117 (3): 531–8. doi:10.1083/jcb.117.3.531. PMC 2289450. PMID 1315316.
  3. ↑ Hoyle J, Phelan JP, Bermingham N, Fisher EM (Nov 1996). "Localization of human and mouse N-ethylmaleimide-sensitive factor (NSF) gene: a two-domain member of the AAA family that is involved in membrane fusion". Mammalian Genome. 7 (11): 850–2. doi:10.1007/s003359900249. PMID 8875895.
  4. ↑ Furst J, Sutton RB, Chen J, Brunger AT, Grigorieff N (Sep 2003). "Electron cryomicroscopy structure of N-ethyl maleimide sensitive factor at 11 A resolution". The EMBO Journal. 22 (17): 4365–74. doi:10.1093/emboj/cdg420. PMC 202363. PMID 12941689.
  5. ↑ Alberts, Bruce (2008). Molecular biology of the cell. Garland Science. ISBN 978-0-8153-4105-5.
  6. ↑ Kuner T, Li Y, Gee KR, Bonewald LF, Augustine GJ (Jan 2008). "Photolysis of a caged peptide reveals rapid action of N-ethylmaleimide sensitive factor before neurotransmitter release". Proceedings of the National Academy of Sciences of the United States of America. 105 (1): 347–52. doi:10.1073/pnas.0707197105. PMC 2224215. PMID 18172208.
  7. ↑ Noel J, Ralph GS, Pickard L, Williams J, Molnar E, Uney JB, Collingridge GL, Henley JM (Jun 1999). "Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism". Neuron. 23 (2): 365–76. doi:10.1016/S0896-6273(00)80786-2. PMID 10399941.
  8. ↑ Glick BS, Rothman JE (1987). "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature. 326 (6110): 309–12. doi:10.1038/326309a0. PMID 3821906.
  9. ↑ Barnard RJ, Morgan A, Burgoyne RD (Nov 1997). "Stimulation of NSF ATPase activity by alpha-SNAP is required for SNARE complex disassembly and exocytosis". The Journal of Cell Biology. 139 (4): 875–83. doi:10.1083/jcb.139.4.875. PMC 2139964. PMID 9362506.
  10. ↑ Hanson PI, Otto H, Barton N, Jahn R (Jul 1995). "The N-ethylmaleimide-sensitive fusion protein and alpha-SNAP induce a conformational change in syntaxin". The Journal of Biological Chemistry. 270 (28): 16955–61. doi:10.1074/jbc.270.28.16955. PMID 7622514.

Further reading

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