title: Retinoic Acid and LTP Recruit Postsynaptic AMPA Receptors Using Distinct SNARE-Dependent Mechanisms.
abstract: Retinoic acid (RA)-dependent homeostatic plasticity and NMDA receptor-dependent long-term potentiation (LTP), a form of Hebbian plasticity, both enhance synaptic strength by increasing the abundance of postsynaptic AMPA receptors (AMPARs). However, it is unclear whether the molecular mechanisms mediating AMPAR trafficking during homeostatic and Hebbian plasticity differ, and it is unknown how RA signaling impacts Hebbian plasticity. Here, we show that RA increases postsynaptic AMPAR abundance using an activity-dependent mechanism that requires a unique SNARE (soluble NSF-attachment protein receptor)-dependent fusion machinery different from that mediating LTP. Specifically, RA-induced AMPAR trafficking did not involve complexin, which activates SNARE complexes containing syntaxin-1 or -3, but not complexes containing syntaxin-4, whereas LTP required complexin. Moreover, RA-induced AMPAR trafficking utilized the Q-SNARE syntaxin-4, whereas LTP utilized syntaxin-3; both additionally required the Q-SNARE SNAP-47 and the R-SNARE synatobrevin-2. Finally, acute RA treatment blocked subsequent LTP expression, probably by increasing AMPAR trafficking. Thus, RA-induced homeostatic plasticity involves a novel, activity-dependent postsynaptic AMPAR-trafficking pathway mediated by a unique SNARE-dependent fusion machinery.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Arendt
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA.
authors.forename: Yingsha
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jurado
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305-5453, USA. Electronic address: luchen1@stanford.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D004357:Drug Synergism; D005089:Exocytosis / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D021381:Protein Transport / Q000502:physiology; D050765:Qa-SNARE Proteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D055366:Synaptic Potentials / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D050765:Qa-SNARE Proteins; D018091:Receptors, AMPA; D050600:SNARE Proteins; C587292:syntaxin 4, human; D014212:Tretinoin
references.citation: Neuron. 2008 Oct 23;60(2):308-20
references.pmid: 18957222
references.citation: Neuropharmacology. 2014 Mar;78:3-12
references.pmid: 23270606
references.citation: Neuron. 2014 Oct 22;84(2):497-510
references.pmid: 25374364
references.citation: Neuron. 2010 Dec 9;68(5):907-20
references.pmid: 21145004
references.citation: Curr Opin Neurobiol. 2011 Feb;21(1):169-74
references.pmid: 20728341
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15951-6
references.pmid: 20733080
references.citation: J Physiol. 1983 Jan;334:33-46
references.pmid: 6306230
references.citation: Annu Rev Physiol. 2015;77:251-70
references.pmid: 25386989
references.citation: Nat Rev Neurosci. 2007 Oct;8(10):755-65
references.pmid: 17882253
references.citation: Nat Neurosci. 2007 Oct;10(10):1235-7
references.pmid: 17873870
references.citation: Genesis. 2002 Feb;32(2):87-90
references.pmid: 11857786
references.citation: Nature. 1995 Jun 1;375(6530):400-4
references.pmid: 7760933
references.citation: Cell. 1995 Oct 6;83(1):111-9
references.pmid: 7553862
references.citation: Curr Opin Neurobiol. 2005 Jun;15(3):334-42
references.pmid: 15922583
references.citation: Annu Rev Neurosci. 2008;31:47-67
references.pmid: 18284372
references.citation: J Neurosci. 2007 Oct 10;27(41):11112-21
references.pmid: 17928453
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20303-8
references.pmid: 19073915
references.citation: J Neurosci. 2007 Apr 25;27(17):4598-602
references.pmid: 17460072
references.citation: Neuron. 2009 Jul 16;63(1):92-105
references.pmid: 19607795
references.citation: J Neurosci. 2008 Jun 4;28(23):6000-9
references.pmid: 18524905
references.citation: Physiol Rev. 2014 Jan;94(1):141-88
references.pmid: 24382885
references.citation: Arch Ital Biol. 2007 Nov;145(3-4):277-87
references.pmid: 18075121
references.citation: Neuron. 1998 Dec;21(6):1353-61
references.pmid: 9883728
references.citation: J Neurosci. 2013 Jan 30;33(5):2087-96
references.pmid: 23365245
references.citation: Neuron. 1995 Aug;15(2):427-34
references.pmid: 7646894
references.citation: J Biol Chem. 2006 Jun 23;281(25):17076-83
references.pmid: 16621800
references.citation: Neuroscience. 2002;115(2):475-82
references.pmid: 12421614
references.citation: Nat Neurosci. 2006 May;9(5):602-4
references.pmid: 16582904
references.citation: J Neurosci. 2010 Jan 6;30(1):242-54
references.pmid: 20053906
references.citation: Biochem Biophys Res Commun. 1992 Dec 15;189(2):1017-23
references.pmid: 1361727
references.citation: Neuron. 2012 Mar 8;73(5):990-1001
references.pmid: 22405208
references.citation: Science. 1998 Jan 16;279(5349):399-403
references.pmid: 9430593
references.citation: J Neurophysiol. 2007 Oct;98(4):2488-92
references.pmid: 17652419
references.citation: Neuron. 2009 Nov 12;64(3):367-80
references.pmid: 19914185
references.citation: Neuron. 2013 Oct 30;80(3):675-90
references.pmid: 24183019
references.citation: Cell. 2001 Jan 12;104(1):71-81
references.pmid: 11163241
references.citation: Int Rev Neurobiol. 2014;117:39-51
references.pmid: 25172628
references.citation: J Neurosci. 2011 Dec 7;31(49):17764-71
references.pmid: 22159093
references.citation: Science. 2006 Aug 4;313(5787):676-80
references.pmid: 16794037
references.citation: EMBO Rep. 2005 Dec;6(12):1137-42
references.pmid: 16319959
references.citation: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16015-20
references.pmid: 18840692
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11714-9
references.pmid: 11553775
references.citation: Mol Brain. 2012;5:8
references.pmid: 22316320
references.citation: Science. 2009 Jan 23;323(5913):516-21
references.pmid: 19164751
references.citation: Mol Cell Biol. 1997 May;17(5):2425-35
references.pmid: 9111311
references.citation: Neuron. 2013 Oct 30;80(3):704-17
references.pmid: 24183021
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):665-74
references.pmid: 18618940
references.citation: Philos Trans R Soc Lond B Biol Sci. 2014 Jan 5;369(1633):20130156
references.pmid: 24298157
references.citation: Cell. 2006 Sep 22;126(6):1175-87
references.pmid: 16990140
references.citation: Neuron. 2013 Feb 6;77(3):542-58
references.pmid: 23395379
references.citation: J Biol Chem. 2000 Jun 30;275(26):19808-18
references.pmid: 10777504
references.citation: Front Mol Neurosci. 2012 Feb 15;5:16
references.pmid: 22419906
references.citation: Science. 2009 Jan 23;323(5913):474-7
references.pmid: 19164740
references.citation: J Neurosci. 2013 Jul 10;33(28):11440-50
references.pmid: 23843516
references.citation: Cell. 2010 Apr 30;141(3):524-35
references.pmid: 20434989
references.citation: Neuron. 2012 Jan 26;73(2):260-7
references.pmid: 22284181
references.citation: Nature. 1998 Feb 26;391(6670):892-6
references.pmid: 9495341
references.citation: Neuron. 2009 Nov 12;64(3):381-90
references.pmid: 19914186
references.citation: Nature. 1992 Oct 29;359(6398):832-5
references.pmid: 1331807