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Sunday Driver links axonal transport to damage signaling
Valeria Cavalli1,
Pekka Kujala2,
Judith Klumperman2, , and
Lawrence S.B. Goldstein1
1 Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093 2 Department of Cell Biology, Universitair Medisch Centrum Utrecht, 3584CX Utrecht, Netherlands
Correspondence to L.S.B. Goldstein: lgoldstein{at}ucsd.edu
Abstract:
Neurons transmit long-range biochemical signals between cellbodies and distant axonal sites or termini. To test the hypothesisthat signaling molecules are hitchhikers on axonal vesicles,we focused on the c-Jun NH2-terminal kinase (JNK) scaffoldingprotein Sunday Driver (syd), which has been proposed to linkthe molecular motor protein kinesin-1 to axonal vesicles. Wefound that syd and JNK3 are present on vesicular structuresin axons, are transported in both the anterograde and retrogradeaxonal transport pathways, and interact with kinesin-I and thedynactin complex. Nerve injury induces local activation of JNK,primarily within axons, and activated JNK and syd are then transportedprimarily retrogradely. In axons, syd and activated JNK colocalizewith p150Glued, a subunit of the dynactin complex, and withdynein. Finally, we found that injury induces an enhanced interactionbetween syd and dynactin. Thus, a mobile axonal JNKsydcomplex may generate a transport-dependent axonal damage surveillancesystem.
P. Kujala's present address is the Netherlands Cancer Institute,1066CX Amsterdam, Netherlands.
Abbreviations used in this paper: APP, amyloid precursor protein;DHC, dynein heavy chain; DIC, dynein intermediate chain; DRG,dorsal root ganglia; JIP, JNK interacting protein; JNK, c-JunNH2-terminal kinase; KLC, kinesin light chain; PNS, postnuclearsupernatant; syd, Sunday Driver.
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