title: LTP requires a unique postsynaptic SNARE fusion machinery.
abstract: Membrane fusion during exocytosis is mediated by assemblies of SNARE (soluble NSF-attachment protein receptor) and SM (Sec1/Munc18-like) proteins. The SNARE/SM proteins involved in vesicle fusion during neurotransmitter release are well understood, whereas little is known about the protein machinery that mediates activity-dependent AMPA receptor (AMPAR) exocytosis during long-term potentiation (LTP). Using direct measurements of LTP in acute hippocampal slices and an in vitro LTP model of stimulated AMPAR exocytosis, we demonstrate that the Q-SNARE proteins syntaxin-3 and SNAP-47 are required for regulated AMPAR exocytosis during LTP but not for constitutive basal AMPAR exocytosis. In contrast, the R-SNARE protein synaptobrevin-2/VAMP2 contributes to both regulated and constitutive AMPAR exocytosis. Both the central complexin-binding and the N-terminal Munc18-binding sites of syntaxin-3 are essential for its postsynaptic role in LTP. Thus, postsynaptic exocytosis of AMPARs during LTP is mediated by a unique fusion machinery that is distinct from that used during presynaptic neurotransmitter release.
authors: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
authors: Sandra
authors: S
authors: Jurado
authors: Debanjan
authors: D
authors: Goswami
authors: Yingsha
authors: Y
authors: Zhang
authors: Alfredo J Miñano
authors: AJ
authors: Molina
authors: Thomas C
authors: TC
authors: Südhof
authors: Robert C
authors: RC
authors: Malenka
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002478:Cells, Cultured; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D018014:Gene Transfer Techniques; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D050765:Qa-SNARE Proteins / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050827:Syntaxin 1 / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005998:Glycine; D050765:Qa-SNARE Proteins; D011810:Quinoxalines; D018091:Receptors, AMPA; D011990:Receptors, Transferrin; D050600:SNARE Proteins; D050827:Syntaxin 1; D050988:Vesicle-Associated Membrane Protein 2; D033921:Vesicular Transport Proteins; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
references: Neuron. 2010 Dec 9;68(5):907-20
references: 21145004
references: Annu Rev Neurosci. 2006;29:325-62
references: 16776589
references: J Biol Chem. 1999 Feb 26;274(9):5649-53
references: 10026182
references: Nat Struct Biol. 1998 Sep;5(9):765-9
references: 9731768
references: Biophys J. 2006 Apr 15;90(8):2843-51
references: 16443657
references: Neuron. 2001 Jan;29(1):243-54
references: 11182095
references: J Neurosci. 2010 Jan 6;30(1):242-54
references: 20053906
references: Neuron. 2004 Sep 30;44(1):5-21
references: 15450156
references: Cell. 2003 Feb 21;112(4):519-33
references: 12600315
references: Neuron. 2008 May 22;58(4):472-97
references: 18498731
references: Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43
references: 16912714
references: Nat Neurosci. 2008 Apr;11(4):457-66
references: 18311135
references: Cell. 2001 Jan 12;104(1):71-81
references: 11163241
references: J Neurosci. 2010 Mar 17;30(11):4132-42
references: 20237283
references: Neuron. 1999 Nov;24(3):649-58
references: 10595516
references: Cell Rep. 2012 Apr 19;1(4):291-8
references: 22832222
references: Nat Struct Mol Biol. 2008 Jul;15(7):665-74
references: 18618940
references: Neuron. 2008 Jan 24;57(2):248-62
references: 18215622
references: Neuron. 2009 Nov 12;64(3):381-90
references: 19914186
references: EMBO J. 2001 May 1;20(9):2202-13
references: 11331586
references: J Biol Chem. 2004 Feb 27;279(9):8403-8
references: 14676208
references: Neuron. 2012 Jul 12;75(1):11-25
references: 22794257
references: Curr Opin Cell Biol. 2010 Aug;22(4):496-505
references: 20561775
references: Neuron. 2005 Dec 22;48(6):977-85
references: 16364901
references: Neuron. 2003 Oct 9;40(2):361-79
references: 14556714
references: Cell. 2007 Jan 12;128(1):183-95
references: 17218264
references: Nat Neurosci. 2007 Oct;10(10):1235-7
references: 17873870
references: Nature. 2001 Mar 1;410(6824):41-9
references: 11242035
references: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16502-9
references: 21953696
references: Science. 1999 Sep 17;285(5435):1870-4
references: 10489359
references: Science. 2001 Nov 2;294(5544):1117-22
references: 11691998
references: Cell. 2008 Oct 31;135(3):535-48
references: 18984164
references: Cell. 1995 Oct 6;83(1):111-9
references: 7553862
references: Biol Psychiatry. 2012 Mar 15;71(6):496-502
references: 21974785
references: Mol Cell Neurosci. 2011 Jan;46(1):1-8
references: 20817097
references: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11388-93
references: 18682558
references: Science. 2007 Aug 24;317(5841):1072-6
references: 17717182
references: Nat Neurosci. 2001 Sep;4(9):917-26
references: 11528423
references: Annu Rev Cell Dev Biol. 2007;23:613-43
references: 17506699
references: Neuron. 2006 Jul 6;51(1):99-111
references: 16815335
references: Nat Rev Neurosci. 2008 Jan;9(1):65-75
references: 18094707
references: Neuron. 2011 Mar 10;69(5):856-75
references: 21382547
references: J Neurosci. 2007 Oct 10;27(41):11112-21
references: 17928453
references: Mol Biol Cell. 2006 Feb;17(2):977-89
references: 16339081
references: Annu Rev Neurosci. 2002;25:103-26
references: 12052905
references: Nat Neurosci. 2010 Mar;13(3):338-43
references: 20118925
references: Nature. 1992 Oct 29;359(6398):832-5
references: 1331807
references: Cell. 2010 Apr 30;141(3):524-35
references: 20434989
references: Cell. 1998 Sep 18;94(6):841-9
references: 9753330
references: Nat Cell Biol. 2011 Jan;13(1):30-9
references: 21151134
references: J Biol Chem. 2000 Jun 30;275(26):19808-18
references: 10777504
references: Nat Rev Neurosci. 2004 Dec;5(12):952-62
references: 15550950
references: Nature. 1993 Sep 9;365(6442):160-3
references: 8103915
references: Science. 2009 Jan 23;323(5913):474-7
references: 19164740
references: J Neurosci. 2007 Nov 7;27(45):12147-55
references: 17989281
references: Neuron. 2009 Nov 12;64(3):367-80
references: 19914185
references: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15951-6
references: 20733080
references: Nat Cell Biol. 2011 Jun;13(6):715-21
references: 21602791
references: Neuron. 2012 Jan 26;73(2):260-7
references: 22284181
references: Science. 1998 Jan 16;279(5349):399-403
references: 9430593
references: Nature. 1998 Sep 24;395(6700):347-53
references: 9759724
references: Neuron. 2009 Jul 16;63(1):92-105
references: 19607795
references: J Neurosci. 2007 Dec 12;27(50):13706-18
references: 18077682
references: Neuron. 2007 Sep 20;55(6):874-89
references: 17880892
references: Annu Rev Neurosci. 2004;27:509-47
references: 15217342
references: Science. 2006 Aug 4;313(5787):676-80
references: 16794037
references: J Neurosci. 2006 Feb 15;26(7):2000-9
references: 16481433
references: Biophys J. 2008 Jun;94(12):4957-70
references: 18326650
references: Cell. 2010 Nov 24;143(5):761-73
references: 21111236
references: J Biol Chem. 2006 Jun 23;281(25):17076-17083
references: 16621800
references: Nat Rev Neurosci. 2007 Nov;8(11):844-58
references: 17948030
references: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7875-80
references: 18505837
references: Science. 2000 Feb 4;287(5454):864-9
references: 10657302
references: Cell. 2006 Sep 22;126(6):1175-87
references: 16990140
references: Science. 2004 Sep 24;305(5692):1972-5
references: 15448273
references: EMBO J. 1994 Nov 1;13(21):5051-61
references: 7957071
references: Neuron. 2000 Nov;28(2):511-25
references: 11144360
references: Trends Neurosci. 2011 May;34(5):258-68
references: 21420743
references: J Biol Chem. 1999 May 28;274(22):15440-6
references: 10336434
references: Biol Psychiatry. 2012 Mar 15;71(6):484-6
references: 22364737
references: Science. 2009 Jan 23;323(5913):516-21
references: 19164751