Sunday Driver links axonal transport to damage signaling
Sunday Driver links axonal transport to damage signaling
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DOI：
10.1083/jcb.200410136
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发表时间：
2005-02-28
影响因子：
7.8
通讯作者：
Goldstein, LSB
中科院分区：
文献类型：
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作者：
Cavalli, V;Kujala, P;Goldstein, LSB
神经元在细胞体和远端轴突位点或末端之间传递长距离生化信号。为了验证信号分子是轴突囊泡上的搭便车者的假设，我们专注于c-Jun NH 2-末端激酶（JNK）支架蛋白Sunday Driver（syd），该蛋白已被提议将分子马达蛋白驱动蛋白-1连接到轴突囊泡。我们发现，Syd和JNK 3存在于轴突的囊泡结构上，在顺行和逆行轴突运输途径中运输，并与驱动蛋白-1和动力蛋白复合物相互作用。神经损伤诱导JNK的局部活化，主要在轴突内，然后活化的JNK和syd主要逆行转运。在轴突中，syd和激活的JNK与p150（Glued）（动力蛋白复合物的亚基）和动力蛋白共定位。最后，我们发现，损伤诱导增强syd和dynactin之间的相互作用。因此，一个移动的轴突JNK-syd复合物可以产生一个依赖于运输的轴突损伤监测系统。
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-1 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 p150(Glued), 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.