title: Dynamics of axonal mRNA transport and implications for peripheral nerve regeneration.
abstract: Locally generating new proteins in subcellular regions provide means to spatially and temporally modify protein content in polarized cells. Recent years have seen resurgence of the concept that axonal processes of neurons can locally synthesize proteins. Experiments from a number of groups have now shown that axonal protein synthesis helps to initiate growth, provides a means to respond to guidance cues, and generates retrograde signaling complexes. Additionally, there is increasing evidence that locally synthesized proteins provide functions beyond injury responses and growth in the mature peripheral nervous system. A key regulatory event in this translational regulation is moving the mRNA templates into the axonal compartment. Transport of mRNAs into axons is a highly regulated and specific process that requires interaction of RNA binding proteins with specific cis-elements or structures within the mRNAs. mRNAs are transported in ribonucleoprotein particles that interact with microtubule motor proteins for long-range axonal transport and likely use microfilaments for short-range movement in the axons. The mature axon is able to recruit mRNAs into translation with injury and possibly other stimuli, suggesting that mRNAs can be stored in a dormant state in the distal axon until needed. Axotomy triggers a shift in the populations of mRNAs localized to axons, indicating a dynamic regulation of the specificity of the axonal transport machinery. In this review, we discuss how axonal mRNA transport and localization are regulated to achieve specific changes in axonal RNA content in response to axonal stimuli.
authors.affiliation: Nemours Biomedical Research, Alfred I. DuPont Hospital for Children, Wilmington, DE 19803, USA.
authors.forename: Soonmoon
authors.initials: S
authors.lastname: Yoo
authors.forename: Erna A
authors.initials: EA
authors.lastname: van Niekerk
authors.forename: Tanuja T
authors.initials: TT
authors.lastname: Merianda
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Twiss
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D008868:Microtubule Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D017711:Nonlinear Dynamics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins
references.citation: Neuron. 2005 Mar 3;45(5):715-26
references.pmid: 15748847
references.citation: J Cell Biol. 1994 Oct;127(2):441-51
references.pmid: 7929587
references.citation: J Neurosci. 2003 Apr 15;23(8):3251-61
references.pmid: 12716932
references.citation: Nat Rev Mol Cell Biol. 2001 Jul;2(7):521-9
references.pmid: 11433366
references.citation: Curr Opin Neurobiol. 2008 Feb;18(1):60-8
references.pmid: 18508259
references.citation: J Neurotrauma. 2006 Mar-Apr;23(3-4):295-308
references.pmid: 16629617
references.citation: J Neurosci Res. 2005 Nov 15;82(4):484-98
references.pmid: 16237720
references.citation: Nat Neurosci. 2006 Oct;9(10):1247-56
references.pmid: 16980963
references.citation: Annu Rev Neurosci. 1994;17:267-310
references.pmid: 8210176
references.citation: J Neurosci. 2009 Jan 21;29(3):638-52
references.pmid: 19158291
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13810-5
references.pmid: 17698811
references.citation: J Neurosci. 1996 Oct 1;16(19):5967-78
references.pmid: 8815879
references.citation: Mol Cell Neurosci. 2009 Oct;42(2):102-115
references.pmid: 19520167
references.citation: J Cell Biol. 2009 Feb 9;184(3):423-35
references.pmid: 19188494
references.citation: J Cell Biol. 2003 Nov 24;163(4):801-12
references.pmid: 14623865
references.citation: Mol Cell Proteomics. 2007 May;6(5):798-811
references.pmid: 17289661
references.citation: Nature. 2005 Nov 24;438(7067):512-5
references.pmid: 16306994
references.citation: Exp Neurol. 2010 May;223(1):5-10
references.pmid: 19699198
references.citation: Nature. 1986 Dec 11-17;324(6097):537-45
references.pmid: 2878369
references.citation: Neuron. 2006 Sep 21;51(6):715-26
references.pmid: 16982418
references.citation: Cell. 1997 Dec 26;91(7):927-38
references.pmid: 9428516
references.citation: Nat Neurosci. 2007 Jul;10(7):828-37
references.pmid: 17529987
references.citation: J Neurosci. 2006 Sep 20;26(38):9743-9
references.pmid: 16988045
references.citation: Science. 1994 Dec 23;266(5193):1996-9
references.pmid: 7801127
references.citation: J Neurosci. 2006 Jul 5;26(27):7135-8
references.pmid: 16822967
references.citation: J Neurosci. 2008 Oct 22;28(43):11024-9
references.pmid: 18945910
references.citation: J Cell Biol. 2003 Jan 6;160(1):77-87
references.pmid: 12507992
references.citation: Curr Opin Neurobiol. 2000 Oct;10(5):587-92
references.pmid: 11084321
references.citation: Science. 2009 Feb 27;323(5918):1208-1211
references.pmid: 19251628
references.citation: Genome Biol. 2002;3(3):REVIEWS0004
references.pmid: 11897027
references.citation: Nat Cell Biol. 2008 Feb;10(2):149-59
references.pmid: 18193038
references.citation: Annu Rev Cell Dev Biol. 2007;23:375-404
references.pmid: 17944572
references.citation: Mol Cell Neurosci. 2009 Apr;40(4):485-95
references.pmid: 19340935
references.citation: Cell. 2009 Feb 20;136(4):719-30
references.pmid: 19239891
references.citation: J Neurosci Res. 1995 Jun 15;41(3):324-34
references.pmid: 7563225
references.citation: Brain Res. 1970 Dec 1;24(2):359-63
references.pmid: 5490299
references.citation: PLoS One. 2008 Apr 09;3(4):e1961
references.pmid: 18398477
references.citation: Neurosci Lett. 1998 Jul 31;251(3):197-200
references.pmid: 9726377
references.citation: J Cell Biol. 2004 Apr 26;165(2):203-11
references.pmid: 15096527
references.citation: J Neurosci. 2008 Jul 23;28(30):7555-62
references.pmid: 18650333
references.citation: J Neuropathol Exp Neurol. 2009 Mar;68(3):326-37
references.pmid: 19225405
references.citation: J Neurosci. 2009 Feb 4;29(5):1514-24
references.pmid: 19193898
references.citation: Curr Opin Neurobiol. 2004 Oct;14(5):574-81
references.pmid: 15464890
references.citation: Mol Cell Neurosci. 2008 Oct;39(2):170-9
references.pmid: 18655836
references.citation: Neuron. 2001 Apr;30(1):227-40
references.pmid: 11343657
references.citation: J Biol Chem. 2004 Dec 10;279(50):52613-22
references.pmid: 15371429
references.citation: Dev Neurobiol. 2007 Aug;67(9):1148-65
references.pmid: 17514713
references.citation: J Neurosci. 2008 Nov 19;28(47):12581-90
references.pmid: 19020050
references.citation: Neuron. 2009 Jan 15;61(1):10-26
references.pmid: 19146809
references.citation: EMBO J. 2006 Oct 18;25(20):4865-76
references.pmid: 17024188
references.citation: Hum Mol Genet. 2002 Jan 1;11(1):93-105
references.pmid: 11773003
references.citation: Cell. 1995 Jan 13;80(1):155-65
references.pmid: 7813012
references.citation: Mol Biol Cell. 2005 Jan;16(1):405-20
references.pmid: 15525674
references.citation: Cell. 2007 Oct 5;131(1):174-87
references.pmid: 17923096
references.citation: Brain Res. 1984 Dec 24;324(2):223-32
references.pmid: 6529618
references.citation: Neuron. 2003 Dec 18;40(6):1095-104
references.pmid: 14687545
references.citation: J Cell Biol. 2007 Sep 10;178(6):965-80
references.pmid: 17785519
references.citation: Trends Biochem Sci. 2007 Jun;32(6):279-85
references.pmid: 17481902
references.citation: Mol Cell. 2007 Mar 9;25(5):635-46
references.pmid: 17349952
references.citation: J Neurosci. 2001 Dec 1;21(23):9291-303
references.pmid: 11717363
references.citation: Science. 2008 Mar 21;319(5870):1668-72
references.pmid: 18309045
references.citation: J Neurosci. 2006 May 24;26(21):5727-32
references.pmid: 16723529
references.citation: Z Zellforsch Mikrosk Anat. 1972;124(2):217-29
references.pmid: 5012671
references.citation: J Neurosci. 2006 Oct 11;26(41):10397-406
references.pmid: 17035524
references.citation: J Cell Biol. 1993 Aug;122(4):825-32
references.pmid: 8349732
references.citation: Nature. 2005 Aug 18;436(7053):1020-1024
references.pmid: 16107849
references.citation: FASEB J. 2007 Mar;21(3):656-70
references.pmid: 17209129
references.citation: Science. 2009 Feb 27;323(5918):1205-8
references.pmid: 19251627
references.citation: Mol Cell Biol. 1997 Apr;17(4):2158-65
references.pmid: 9121465
references.citation: RNA. 2007 May;13(5):625-42
references.pmid: 17449729
references.citation: J Neurochem. 2004 May;89(3):613-26
references.pmid: 15086518
references.citation: J Cell Biol. 2007 Oct 8;179(1):139-49
references.pmid: 17923533
references.citation: Genes Dev. 2003 Mar 1;17(5):638-53
references.pmid: 12629046
references.citation: Neuroscience. 2009 Mar 17;159(2):647-56
references.pmid: 19171178
references.citation: J Neurosci. 2009 Apr 15;29(15):4697-707
references.pmid: 19369540
references.citation: Neuron. 2008 Jul 31;59(2):241-52
references.pmid: 18667152
references.citation: J Neurosci. 2008 Dec 17;28(51):13793-804
references.pmid: 19091970
references.citation: J Neurosci. 2006 Jun 14;26(24):6496-508
references.pmid: 16775137
references.citation: J Neurosci. 2005 Jan 26;25(4):778-91
references.pmid: 15673657
references.citation: J Cell Biol. 1993 Oct;123(1):165-72
references.pmid: 8408195
references.citation: Neural Dev. 2009 Mar 02;4:8
references.pmid: 19254368
references.citation: Trends Neurosci. 2002 Aug;25(8):400-4
references.pmid: 12127756
references.citation: Neuron. 2002 Aug 29;35(5):907-20
references.pmid: 12372285
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7045-50
references.pmid: 11416185
references.citation: J Cell Biol. 2003 Sep 1;162(5):919-31
references.pmid: 12952942
references.citation: J Cell Sci. 2009 Mar 1;122(Pt 5):587-93
references.pmid: 19225125
references.citation: J Neurosci. 2000 Nov 15;20(22):8390-400
references.pmid: 11069946
references.citation: J Biol Chem. 2002 Aug 2;277(31):27996-8002
references.pmid: 12034726
references.citation: Nature. 1996 Feb 22;379(6567):746-9
references.pmid: 8602224
references.citation: Nat Rev Mol Cell Biol. 2008 Dec;9(12):971-80
references.pmid: 19023284
references.citation: Exp Neurol. 2010 May;223(1):28-37
references.pmid: 19520073
references.citation: Nat Genet. 2006 Feb;38(2):197-202
references.pmid: 16429158
references.citation: J Neurosci. 2004 Jul 7;24(27):6161-70
references.pmid: 15240808
references.citation: J Cell Biol. 1999 Oct 4;147(1):59-70
references.pmid: 10508855
references.citation: Eur J Neurosci. 2007 Jan;25(2):341-50
references.pmid: 17284174
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11239-44
references.pmid: 17595294
references.citation: J Cell Biol. 2006 Mar 13;172(6):803-8
references.pmid: 16520386
references.citation: Neuron. 2006 Jan 19;49(2):215-28
references.pmid: 16423696
references.citation: Trends Cell Biol. 2009 May;19(5):236-43
references.pmid: 19359177
references.citation: Nature. 1996 Feb 22;379(6567):694-9
references.pmid: 8602214
references.citation: Cell. 1987 Feb 13;48(3):465-78
references.pmid: 2433048
references.citation: Dev Cell. 2008 Jun;14(6):926-39
references.pmid: 18539120
references.citation: J Neurosci. 1994 Mar;14(3 Pt 1):1130-40
references.pmid: 7509864
references.citation: J Neurosci. 1996 Feb 15;16(4):1400-11
references.pmid: 8778291
references.citation: Neurology. 2006 Nov 14;67(9):1710-2
references.pmid: 17101916
references.citation: J Neurobiol. 2004 Nov;61(2):222-35
references.pmid: 15389607
references.citation: J Neurosci. 1982 Mar;2(3):284-91
references.pmid: 7062109
references.citation: Mol Cell Proteomics. 2006 Apr;5(4):635-51
references.pmid: 16352523
references.citation: Cell. 1992 Jan 24;68(2):201-19
references.pmid: 1733499
references.citation: Nat Rev Mol Cell Biol. 2005 May;6(5):363-75
references.pmid: 15852043
references.citation: Nat Neurosci. 2006 Oct;9(10):1265-73
references.pmid: 16980965
references.citation: Neuron. 2001 Aug 2;31(2):261-75
references.pmid: 11502257
references.citation: J Neurosci. 1998 Jan 1;18(1):251-65
references.pmid: 9412505