title: Syntaxin13 expression is regulated by mammalian target of rapamycin (mTOR) in injured neurons to promote axon regeneration.
abstract: Injured peripheral neurons successfully activate intrinsic signaling pathways to enable axon regeneration. We have previously shown that dorsal root ganglia (DRG) neurons activate the mammalian target of rapamycin (mTOR) pathway following injury and that this activity enhances their axon growth capacity. mTOR plays a critical role in protein synthesis, but the mTOR-dependent proteins enhancing the regenerative capacity of DRG neurons remain unknown. To identify proteins whose expression is regulated by injury in an mTOR-dependent manner, we analyzed the protein composition of DRGs from mice in which we genetically activated mTOR and from mice with or without a prior nerve injury. Quantitative label-free mass spectrometry analyses revealed that the injury effects were correlated with mTOR activation. We identified a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family of proteins, syntaxin13, whose expression was increased by injury in an mTOR-dependent manner. Increased syntaxin13 levels in injured nerves resulted from local protein synthesis and not axonal transport. Finally, knockdown of syntaxin13 in cultured DRG neurons prevented axon growth and regeneration. Together, these data suggest that syntaxin13 translation is regulated by mTOR in injured neurons to promote axon regeneration.
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Cho
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Liberto
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Dan
authors.initials: D
authors.lastname: Carlin
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Namiko
authors.initials: N
authors.lastname: Abe
authors.affiliation: the Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94158-2517, and.
authors.forename: Kathy H
authors.initials: KH
authors.lastname: Li
authors.affiliation: the Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94158-2517, and.
authors.forename: Alma L
authors.initials: AL
authors.lastname: Burlingame
authors.affiliation: the Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California at San Francisco, San Francisco, California 94158-2517, and.
authors.forename: Shenheng
authors.initials: S
authors.lastname: Guan
authors.affiliation: the Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Izhak
authors.initials: I
authors.lastname: Michaelevski
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St. Louis, Missouri 63110, cavalli@pcg.wustl.edu.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D019771:Axotomy; D002478:Cells, Cultured; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*; D040901:Proteomics; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D050765:Qa-SNARE Proteins; C496153:syntaxin 12, mouse; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: Axon; Proteomics; Regeneration; SNARE Proteins; mTOR
references.citation: Nature. 2012 May 02;485(7396):109-13
references.pmid: 22552098
references.citation: Eur J Neurosci. 2000 Jun;12(6):1913-23
references.pmid: 10886332
references.citation: J Neurosci. 1989 Oct;9(10):3505-12
references.pmid: 2552034
references.citation: Genes Dev. 2008 Sep 15;22(18):2447-53
references.pmid: 18794342
references.citation: Brain Res. 1970 Sep 29;23(1):1-21
references.pmid: 4919474
references.citation: J Neurosci. 2012 Jul 25;32(30):10352-64
references.pmid: 22836268
references.citation: Proc Natl Acad Sci U S A. 1990 Feb;87(4):1561-5
references.pmid: 1689489
references.citation: Cell. 2013 Nov 7;155(4):894-908
references.pmid: 24209626
references.citation: Nat Neurosci. 2013 Feb;16(2):166-73
references.pmid: 23292679
references.citation: J Neurobiol. 1993 Jul;24(7):959-70
references.pmid: 8228973
references.citation: Genes Dev. 2008 Sep 15;22(18):2485-95
references.pmid: 18794346
references.citation: Biochim Biophys Acta. 2000 Jun 26;1486(1):84-96
references.pmid: 10856715
references.citation: J Physiol. 1969 Apr;201(2):80P-81P
references.pmid: 5780576
references.citation: Cell. 2002 Jul 26;110(2):223-35
references.pmid: 12150930
references.citation: Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43
references.pmid: 16912714
references.citation: J Neurosci. 2010 Sep 1;30(35):11654-69
references.pmid: 20810886
references.citation: J Neurosci. 2009 Apr 29;29(17):5546-57
references.pmid: 19403822
references.citation: Neuron. 2001 Dec 20;32(6):1013-26
references.pmid: 11754834
references.citation: Brain Res. 2009 Jan 28;1251:65-79
references.pmid: 19022228
references.citation: J Neurosci. 2006 Apr 26;26(17):4630-7
references.pmid: 16641243
references.citation: PLoS One. 2008 Apr 09;3(4):e1961
references.pmid: 18398477
references.citation: J Neurosci. 1999 Dec 1;19(23):10324-37
references.pmid: 10575030
references.citation: Commun Integr Biol. 2010 May;3(3):209-14
references.pmid: 20714395
references.citation: J Biol Chem. 2004 May 7;279(19):20471-9
references.pmid: 14993220
references.citation: EMBO J. 2012 Jun 12;31(14):3063-78
references.pmid: 22692128
references.citation: J Neurochem. 2013 Sep;126(6):792-804
references.pmid: 23586486
references.citation: J Neurosci. 2005 Jan 12;25(2):331-42
references.pmid: 15647476
references.citation: Nat Neurosci. 2010 Feb;13(2):163-72
references.pmid: 20062052
references.citation: Nat Commun. 2014 Mar 25;5:3506
references.pmid: 24667291
references.citation: J Biol Chem. 2009 Dec 11;284(50):34628-39
references.pmid: 19801628
references.citation: Int Rev Neurobiol. 1971;14:49-124
references.pmid: 4948651
references.citation: J Neurosci. 2013 Feb 20;33(8):3311-22
references.pmid: 23426659
references.citation: Nature. 2005 Aug 18;436(7053):1020-1024
references.pmid: 16107849
references.citation: Neuron. 2012 Jun 21;74(6):1015-22
references.pmid: 22726832
references.citation: Annu Rev Neurosci. 2011;34:131-52
references.pmid: 21438684
references.citation: J Biol Chem. 2010 Sep 3;285(36):28034-43
references.pmid: 20615870
references.citation: Anal Chem. 1999 Jul 15;71(14):2871-82
references.pmid: 10424174
references.citation: J Cell Sci. 2013 Jan 1;126(Pt 1):90-102
references.pmid: 23097042
references.citation: Nat Neurosci. 2010 Sep;13(9):1075-81
references.pmid: 20694004
references.citation: Mol Cell Proteomics. 2008 Dec;7(12):2386-98
references.pmid: 18653769
references.citation: J Neurosci. 2005 Jan 26;25(4):778-91
references.pmid: 15673657
references.citation: Cell Tissue Res. 2012 Jul;349(1):119-32
references.pmid: 22350947
references.citation: Science. 2008 Nov 7;322(5903):963-6
references.pmid: 18988856
references.citation: Traffic. 2011 Sep;12(9):1099-108
references.pmid: 21535338
references.citation: J Neurobiol. 2000 Jul;44(1):72-81
references.pmid: 10880133
references.citation: Nat Rev Neurosci. 2014 Jan;15(1):32-42
references.pmid: 24326686
references.citation: J Cell Biol. 2005 Feb 28;168(5):775-87
references.pmid: 15738268
references.citation: Curr Opin Cell Biol. 2004 Aug;16(4):400-6
references.pmid: 15261672
references.citation: BMC Cell Biol. 2010 Aug 10;11:62
references.pmid: 20698987
references.citation: Mol Cell Proteomics. 2011 Dec;10(12):M111.010728
references.pmid: 21937731
references.citation: Exp Neurol. 2010 May;223(1):28-37
references.pmid: 19520073
references.citation: RNA. 2011 Jan;17(1):85-98
references.pmid: 21098654
references.citation: Trends Neurosci. 1996 Apr;19(4):144-9
references.pmid: 8658598
references.citation: Mol Cell Neurosci. 2009 Feb;40(2):128-42
references.pmid: 19022387
references.citation: J Physiol. 1968 Jun;196(3):655-76
references.pmid: 5664236
references.citation: J Cell Biol. 1998 Nov 16;143(4):957-71
references.pmid: 9817754
references.citation: Trends Cell Biol. 2009 Jul;19(7):317-24
references.pmid: 19540123