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The regeneration of damaged nerves relies on a JNK-dependent MAPK pathway and the stress-responsive transcription factor it activates, c-Jun. In relatively small epithelial cells, JNK can simply diffuse to the nucleus to turn on c-Jun. But human neurons can be up to a meter long—too long for diffusion to suffice. On page 775, Cavalli et al. suggest that damage communication might be achieved quickly by hooking JNK to axonal vesicles.JNK interacts with a scaffold protein called Sunday Driver (syd). Syd, in turn, has been proposed to link vesicles to the microtubule motor protein kinesin. With this knowledge in hand, the group now shows that JNK is a surveillance molecule ready to detect and report axonal injuries to the cell body.) X2 a: F9 T/ ^* `7 G5 m, {2 e' g
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JNK and syd were found in murine axons on vesicles that were traveling both out to axon tips (on kinesin motors) and back to the cell body (on dynein). Injuries activated JNK out in axons and enhanced its interaction with the dynein-associated complex dynactin. Axonal injuries are thus expected to bring active JNK to the cell body, where it can turn on c-Jun to start the repair process.
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% L6 G0 v K" |8 Y8 c# c1 H9 L) FOther molecules in complex with JNK may keep the kinase in its activated form for the long trip, either by protecting JNK's initial phosphorylation or by repeatedly phosphorylating it. As yet, though, it is unclear what other proteins reside in the vesicles. JNK and syd may be simply hitchhiking on vesicles that are transporting synaptic proteins. Alternatively, the vesicles may be dedicated damage repair packages. A cell culture model will be most helpful for the biochemistry that needs to be done next.( t0 l3 f1 l0 ^, M
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Neurons may be an extreme version of a problem that also exists in smaller cells. Although microtubules are not absolutely required for injury responses in epithelial cells, a motor-based transport mechanism may be used normally to improve repair efficiency.(Active JNK (green) rides with dynein (re) |
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发表于 2009-3-6 08:57
发表于 2015-6-19 15:10
