title: In vivo quantitative proteomics of somatosensory cortical synapses shows which protein levels are modulated by sensory deprivation.
abstract: Postnatal bilateral whisker trimming was used as a model system to test how synaptic proteomes are altered in barrel cortex by sensory deprivation during synaptogenesis. Using quantitative mass spectrometry, we quantified more than 7,000 synaptic proteins and identified 89 significantly reduced and 161 significantly elevated proteins in sensory-deprived synapses, 22 of which were validated by immunoblotting. More than 95% of quantified proteins, including abundant synaptic proteins such as PSD-95 and gephyrin, exhibited no significant difference under high- and low-activity rearing conditions, suggesting no tissue-wide changes in excitatory or inhibitory synaptic density. In contrast, several proteins that promote mature spine morphology and synaptic strength, such as excitatory glutamate receptors and known accessory factors, were reduced significantly in deprived synapses. Immunohistochemistry revealed that the reduction in SynGAP1, a postsynaptic scaffolding protein, was restricted largely to layer I of barrel cortex in sensory-deprived rats. In addition, protein-degradation machinery such as proteasome subunits, E2 ligases, and E3 ligases, accumulated significantly in deprived synapses, suggesting targeted synaptic protein degradation under sensory deprivation. Importantly, this screen identified synaptic proteins whose levels were affected by sensory deprivation but whose synaptic roles have not yet been characterized in mammalian neurons. These data demonstrate the feasibility of defining synaptic proteomes under different sensory rearing conditions and could be applied to elucidate further molecular mechanisms of sensory development.
authors: Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, USA.
authors: Margaret T
authors: MT
authors: Butko
authors: Jeffrey N
authors: JN
authors: Savas
authors: Beth
authors: B
authors: Friedman
authors: Claire
authors: C
authors: Delahunty
authors: Ford
authors: F
authors: Ebner
authors: John R
authors: JR
authors: Yates
authors: Roger Y
authors: RY
authors: Tsien
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D051379:Mice; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D040901:Proteomics; D012683:Sensory Deprivation; D013569:Synapses; D053719:Tandem Mass Spectrometry
chemical_list: D009419:Nerve Tissue Proteins
references: Biophys J. 2010 Jun 16;98(12):2867-76
references: 20550899
references: Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16994-8
references: 20837545
references: Nat Neurosci. 2012 Dec;15(12):1742-51
references: 23103964
references: Neuron. 2011 Dec 8;72(5):789-805
references: 22153375
references: Biol Psychiatry. 2011 May 1;69(9):898-901
references: 21237447
references: Nature. 2012 Mar 18;484(7393):237-41
references: 22426000
references: J Neurosci. 2009 Aug 5;29(31):9778-93
references: 19657031
references: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1340-5
references: 12552130
references: J Neurosci. 2007 Jul 11;27(28):7365-76
references: 17626197
references: J Comp Neurol. 2010 May 15;518(10):1711-23
references: 20235164
references: J Neurochem. 2011 Oct;119(1):27-39
references: 21338354
references: J Biol Chem. 2009 Dec 25;284(52):36521-36534
references: 19861419
references: Cell. 2012 Nov 9;151(4):709-723
references: 23141534
references: Neuron. 2012 Jan 26;73(2):391-404
references: 22284191
references: Neuron. 2011 Sep 8;71(5):869-82
references: 21903080
references: Int J Biochem Cell Biol. 2012 Jun;44(6):825-9
references: 22405938
references: Nature. 1997 Feb 6;385(6616):533-6
references: 9020359
references: EMBO J. 2007 Apr 18;26(8):2029-40
references: 17380122
references: Nat Neurosci. 2011 Jun;14(6):744-9
references: 21602822
references: J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89
references: 24226387
references: J Neurosci. 2008 Dec 10;28(50):13673-83
references: 19074040
references: Dev Neurobiol. 2010 Nov;70(13):875-83
references: 20669324
references: Eur J Neurosci. 2008 Jan;27(2):315-25
references: 18215230
references: Neuron. 2003 Jun 19;38(6):965-76
references: 12818181
references: J Neurosci. 2008 Feb 13;28(7):1697-708
references: 18272690
references: Anal Chem. 2003 Dec 15;75(24):6912-21
references: 14670053
references: Neuroscience. 2002;111(4):799-814
references: 12031405
references: Neuron. 2012 Mar 8;73(5):903-10
references: 22405201
references: Neuron. 2004 Jun 10;42(5):789-801
references: 15182718
references: Cell. 1999 Oct 1;99(1):59-69
references: 10520994
references: Mol Cell Proteomics. 2006 Jun;5(6):1158-70
references: 16507876
references: PLoS Biol. 2011 Jan 18;9(1):e1000582
references: 21267068
references: J Neurosci. 2011 Jan 5;31(1):89-96
references: 21209193
references: Neuron. 2009 Jul 16;63(1):12-26
references: 19607789
references: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12113-8
references: 21724987
references: J Neurosci. 2011 Apr 20;31(16):6174-87
references: 21508241
references: Nat Rev Neurosci. 2010 May;11(5):301-15
references: 20389305
references: J Proteome Res. 2007 May;6(5):2005-10
references: 17375949
references: J Neurosci. 2010 Dec 8;30(49):16718-29
references: 21148011
references: PLoS One. 2010 Mar 24;5(3):e9842
references: 20352094
references: Neuron. 2012 Apr 26;74(2):374-83
references: 22542189
references: Nat Rev Neurosci. 2011 Jan;12(1):9-15
references: 21119699
references: Neuron. 2011 Sep 22;71(6):1102-15
references: 21943606
references: Nat Neurosci. 2003 Mar;6(3):291-9
references: 12577061
references: J Neurosci. 2006 Feb 22;26(8):2184-96
references: 16495445
references: Curr Opin Neurobiol. 2008 Oct;18(5):524-31
references: 18834940
references: Eur J Neurosci. 2010 Feb;31(3):529-43
references: 20105235
references: Cell. 1993 Dec 31;75(7):1263-71
references: 8269510
references: Science. 2011 Nov 4;334(6056):623-8
references: 22053042
references: Science. 2012 Feb 24;335(6071):942
references: 22300851
references: Nat Biotechnol. 2001 Mar;19(3):242-7
references: 11231557
references: FEBS Lett. 2009 Dec 17;583(24):3966-73
references: 19850042
references: J Neurosci. 2006 Feb 8;26(6):1776-86
references: 16467526
references: Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11834-8
references: 8524859
references: Development. 2011 Jul;138(14):3079-90
references: 21693523
references: Trends Biochem Sci. 2011 Jul;36(7):388-96
references: 21616670
references: J Proteome Res. 2007 Mar;6(3):1059-71
references: 17330943
references: Neuron. 2011 May 26;70(4):758-72
references: 21609830
references: J Neurosci. 2003 Jan 1;23(1):358-66
references: 12514235
references: Mol Brain. 2012 May 14;5:14
references: 22583753
references: J Proteome Res. 2012 Apr 6;11(4):2467-79
references: 22397461
references: Nat Rev Neurosci. 2012 May 10;13(6):365-79
references: 22573027
references: Neuron. 2003 Apr 24;38(2):277-89
references: 12718861
references: Annu Rev Neurosci. 2009;32:33-55
references: 19400721
references: J Biol Chem. 2010 Sep 10;285(37):28674-82
references: 20615874
references: Curr Protoc Bioinformatics. 2007 Jan;Chapter 13:Unit 13.4
references: 18428785
references: Neuron. 2012 May 10;74(3):453-66
references: 22578497
references: Cereb Cortex. 2014 Feb;24(2):521-31
references: 23118196
references: Cell. 2006 Oct 6;127(1):49-58
references: 17018276
references: J Neurosci. 2008 Apr 2;28(14):3604-14
references: 18385319
references: FEBS Lett. 2007 Oct 2;581(24):4754-60
references: 17868671
references: Mol Neurobiol. 2009 Aug;40(1):46-54
references: 19401831
references: J Neurosci. 2009 Apr 29;29(17):5587-96
references: 19403825
references: J Struct Biol. 2008 Mar;161(3):359-71
references: 17962040
references: Neural Plast. 2012;2012:728161
references: 22548195
references: Can J Physiol Pharmacol. 1997 May;75(5):470-8
references: 9250380
references: J Proteome Res. 2002 Jan-Feb;1(1):21-6
references: 12643522
references: J Cereb Blood Flow Metab. 2004 Jul;24(7):744-55
references: 15241182
references: Science. 2001 Nov 2;294(5544):1030-8
references: 11691980
references: Nat Biotechnol. 1999 Jul;17(7):676-82
references: 10404161
references: Genome Res. 2007 Sep;17(9):1378-88
references: 17675365
references: J Neurosci. 2005 Jul 27;25(30):6984-96
references: 16049174
references: Neuroscience. 2010 Dec 29;171(4):951-72
references: 20884330
references: Acta Pharmacol Sin. 2004 May;25(5):602-10
references: 15132826
references: Rapid Commun Mass Spectrom. 2004;18(18):2162-8
references: 15317041
references: Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7744-9
references: 18511556
references: Nature. 2005 Jul 14;436(7048):261-5
references: 16015331
references: Brain Res Dev Brain Res. 1990 Mar 1;52(1-2):294-7
references: 2331798
references: Cell. 2004 Oct 15;119(2):245-56
references: 15479641
references: J Cell Sci. 2012 May 1;125(Pt 9):2235-43
references: 22344257
references: Neuron. 2001 Feb;29(2):485-96
references: 11239437
references: J Neurosci. 2007 Mar 7;27(10):2673-82
references: 17344405
references: Eur J Neurosci. 2011 Aug;34(3):362-73
references: 21722213
references: Anal Chem. 2005 Dec 1;77(23):7646-53
references: 16316172
references: Curr Opin Neurobiol. 2004 Feb;14(1):89-95
references: 15018943
references: Nature. 2012 Mar 18;484(7393):201-7
references: 22425994
references: Cell. 2009 Sep 18;138(6):1222-35
references: 19766573
references: J Proteome Res. 2003 Jan-Feb;2(1):43-50
references: 12643542
references: Brain Res. 2012 Jan 30;1435:1-7
references: 22197698
references: Neuron. 2001 May;30(2):489-502
references: 11395009
references: J Neurosci. 2006 Feb 1;26(5):1355-65
references: 16452659
references: J Neurosci. 1998 Dec 1;18(23):10196-206
references: 9822773
references: Science. 2003 Mar 7;299(5612):1585-8
references: 12624270
references: PLoS Genet. 2006 Sep 29;2(9):e124
references: 17009871
references: Cell. 2008 Oct 31;135(3):401-6
references: 18984149
references: Neuroscience. 2009 Jan 12;158(1):78-88
references: 18304748