title: Sunday Driver links axonal transport to damage signaling.
abstract: Neurons transmit long-range biochemical signals between cell bodies and distant axonal sites or termini. To test the hypothesis that signaling molecules are hitchhikers on axonal vesicles, we focused on the c-Jun NH2-terminal kinase (JNK) scaffolding protein Sunday Driver (syd), which has been proposed to link the molecular motor protein kinesin-1 to axonal vesicles. We found that syd and JNK3 are present on vesicular structures in axons, are transported in both the anterograde and retrograde axonal transport pathways, and interact with kinesin-I and the dynactin complex. Nerve injury induces local activation of JNK, primarily within axons, and activated JNK and syd are then transported primarily retrogradely. In axons, syd and activated JNK colocalize with p150Glued, a subunit of the dynactin complex, and with dynein. Finally, we found that injury induces an enhanced interaction between syd and dynactin. Thus, a mobile axonal JNK-syd complex may generate a transport-dependent axonal damage surveillance system.
authors.affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
authors.forename: Pekka
authors.initials: P
authors.lastname: Kujala
authors.forename: Judith
authors.initials: J
authors.lastname: Klumperman
authors.forename: Lawrence S B
authors.initials: LS
authors.lastname: Goldstein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D005455:Fluorescent Antibody Technique; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D021381:Protein Transport / Q000502:physiology; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000601:surgery; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D000072159:Dynactin Complex; C403619:Mapk8ip3 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C417671:syd protein, Drosophila; D048057:Mitogen-Activated Protein Kinase 10
references.citation: Mol Cell Biol. 2000 Feb;20(3):1030-43
references.pmid: 10629060
references.citation: J Neurosci. 1998 Feb 15;18(4):1318-28
references.pmid: 9454841
references.citation: Cell. 2000 Oct 13;103(2):239-52
references.pmid: 11057897
references.citation: Exp Neurol. 2000 Dec;166(2):392-402
references.pmid: 11085904
references.citation: Science. 2000 Nov 24;290(5496):1574-7
references.pmid: 11090355
references.citation: Cell. 2000 Nov 10;103(4):583-94
references.pmid: 11106729
references.citation: Neuron. 2000 Nov;28(2):449-59
references.pmid: 11144355
references.citation: J Neurosci. 2001 Feb 1;21(3):RC125
references.pmid: 11157096
references.citation: J Cell Biol. 2001 Mar 5;152(5):959-70
references.pmid: 11238452
references.citation: J Neuroimmunol. 2001 Mar 1;114(1-2):48-56
references.pmid: 11240015
references.citation: J Neurobiol. 2001 Apr;47(1):67-79
references.pmid: 11257614
references.citation: J Biol Chem. 2001 Apr 13;276(15):11821-9
references.pmid: 11096106
references.citation: Genes Dev. 2001 Sep 15;15(18):2421-32
references.pmid: 11562351
references.citation: Mol Cell Neurosci. 1998 Oct;12(3):105-18
references.pmid: 9790733
references.citation: Curr Opin Cell Biol. 1999 Feb;11(1):45-53
references.pmid: 10047518
references.citation: Neuron. 1999 Apr;22(4):667-76
references.pmid: 10230788
references.citation: Mol Cell Biol. 1999 Oct;19(10):7245-54
references.pmid: 10490659
references.citation: Mol Cell Biol. 1999 Nov;19(11):7539-48
references.pmid: 10523642
references.citation: Neuron. 2001 Dec 6;32(5):787-800
references.pmid: 11738026
references.citation: J Cell Biol. 2002 Feb 18;156(4):715-24
references.pmid: 11854311
references.citation: Nature. 2002 May 2;417(6884):83-7
references.pmid: 11986669
references.citation: J Cell Biol. 2002 May 13;157(4):679-91
references.pmid: 12011113
references.citation: J Neurobiol. 2002 Jun 15;51(4):302-12
references.pmid: 12150505
references.citation: J Biol Chem. 2002 Oct 4;277(40):37693-701
references.pmid: 12167659
references.citation: J Cell Biol. 2003 Feb 3;160(3):297-301
references.pmid: 12551954
references.citation: Dev Cell. 2003 Apr;4(4):521-33
references.pmid: 12689591
references.citation: J Cell Biol. 2003 Apr 14;161(1):55-66
references.pmid: 12682084
references.citation: Brain. 2003 Jul;126(Pt 7):1671-82
references.pmid: 12805110
references.citation: Neuron. 2003 Jul 3;39(1):69-84
references.pmid: 12848933
references.citation: J Neurobiol. 2003 Nov;57(2):204-20
references.pmid: 14556286
references.citation: Neurosci Lett. 2003 Nov 20;351(3):181-5
references.pmid: 14623136
references.citation: Neuron. 2003 Dec 18;40(6):1095-104
references.pmid: 14687545
references.citation: J Neurobiol. 2004 Feb 5;58(2):287-94
references.pmid: 14704959
references.citation: Gene. 2004 Mar 31;329:51-60
references.pmid: 15033528
references.citation: J Comp Neurol. 2004 Jul 5;474(4):535-45
references.pmid: 15174071
references.citation: Neuron. 2004 Jul 8;43(1):57-67
references.pmid: 15233917
references.citation: J Neurosci. 2004 Aug 25;24(34):7583-95
references.pmid: 15329406
references.citation: J Cell Biol. 1980 Mar;84(3):513-30
references.pmid: 6153657
references.citation: J Biol Chem. 1981 Feb 25;256(4):1604-7
references.pmid: 6257680
references.citation: Nature. 1987 Nov 12-18;330(6144):181-3
references.pmid: 3670402
references.citation: J Cell Biol. 1991 Apr;113(1):123-35
references.pmid: 2007617
references.citation: Neurosci Lett. 1991 Aug 5;129(1):107-10
references.pmid: 1922958
references.citation: Brain Res. 1991 Dec 6;566(1-2):198-207
references.pmid: 1726060
references.citation: J Cell Biol. 1995 Jul;130(1):149-56
references.pmid: 7540615
references.citation: Brain Res. 1995 Aug 28;690(1):55-63
references.pmid: 7496807
references.citation: Mol Neurobiol. 1996 Aug;13(1):61-79
references.pmid: 8892336
references.citation: Trends Neurosci. 1997 May;20(5):227-31
references.pmid: 9141200
references.citation: J Neurobiol. 1997 Aug;33(2):151-60
references.pmid: 9240371
references.citation: Nature. 1997 Oct 23;389(6653):865-70
references.pmid: 9349820
references.citation: EMBO J. 1998 Jan 2;17(1):149-58
references.pmid: 9427749
references.citation: J Neurosci. 1999 Sep 15;19(18):RC24
references.pmid: 10479717