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Sunday Driver links axonal transport to damage signaling.

Cavalli V, Kujala P, Klumperman J, Goldstein LS - J. Cell Biol. (2005)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.

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.

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Syd interacts with the dynactin complex. (A and B) Coimmunoprecipitation from sciatic nerve extract was probed with the indicated antibodies. A subunit of the dynactin complex, p150Glued, coimmunoprecipitates with syd. The reverse experiment shows coimmunoprecipitation of syd with KLC, p50, and p150Glued. (C and D) Deconvoluted images of sciatic nerve longitudinal sections show partial colocalization (arrowheads) between syd and p150Glued and between syd and DHC within a single axon (stained with the neurofilament marker SMI31). Bars, 2 μm.
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fig4: Syd interacts with the dynactin complex. (A and B) Coimmunoprecipitation from sciatic nerve extract was probed with the indicated antibodies. A subunit of the dynactin complex, p150Glued, coimmunoprecipitates with syd. The reverse experiment shows coimmunoprecipitation of syd with KLC, p50, and p150Glued. (C and D) Deconvoluted images of sciatic nerve longitudinal sections show partial colocalization (arrowheads) between syd and p150Glued and between syd and DHC within a single axon (stained with the neurofilament marker SMI31). Bars, 2 μm.

Mentions: The observation of a retrograde pool of syd raised the possibility that syd interacts with the dynein/dynactin retrograde motor system. Coimmunoprecipitation experiments from sciatic nerve extracts showed that syd interacts with dynamitin (p50) and p150Glued, two subunits of the dynactin complex (Fig. 4, A and B). Syd also interacts with kinesin light chain (KLC; Fig. 4 B), as shown previously (Bowman et al., 2000). We did not observe interaction between KLC or kinesin heavy chain (KIF5C) and p50 or p150Glued, suggesting that syd binds either kinesin or dynactin, but not both simultaneously.


Sunday Driver links axonal transport to damage signaling.

Cavalli V, Kujala P, Klumperman J, Goldstein LS - J. Cell Biol. (2005)

Syd interacts with the dynactin complex. (A and B) Coimmunoprecipitation from sciatic nerve extract was probed with the indicated antibodies. A subunit of the dynactin complex, p150Glued, coimmunoprecipitates with syd. The reverse experiment shows coimmunoprecipitation of syd with KLC, p50, and p150Glued. (C and D) Deconvoluted images of sciatic nerve longitudinal sections show partial colocalization (arrowheads) between syd and p150Glued and between syd and DHC within a single axon (stained with the neurofilament marker SMI31). Bars, 2 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171809&req=5

fig4: Syd interacts with the dynactin complex. (A and B) Coimmunoprecipitation from sciatic nerve extract was probed with the indicated antibodies. A subunit of the dynactin complex, p150Glued, coimmunoprecipitates with syd. The reverse experiment shows coimmunoprecipitation of syd with KLC, p50, and p150Glued. (C and D) Deconvoluted images of sciatic nerve longitudinal sections show partial colocalization (arrowheads) between syd and p150Glued and between syd and DHC within a single axon (stained with the neurofilament marker SMI31). Bars, 2 μm.
Mentions: The observation of a retrograde pool of syd raised the possibility that syd interacts with the dynein/dynactin retrograde motor system. Coimmunoprecipitation experiments from sciatic nerve extracts showed that syd interacts with dynamitin (p50) and p150Glued, two subunits of the dynactin complex (Fig. 4, A and B). Syd also interacts with kinesin light chain (KLC; Fig. 4 B), as shown previously (Bowman et al., 2000). We did not observe interaction between KLC or kinesin heavy chain (KIF5C) and p50 or p150Glued, suggesting that syd binds either kinesin or dynactin, but not both simultaneously.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA.

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.

Show MeSH
Related in: MedlinePlus