期刊
SCIENCE SIGNALING
卷 3, 期 130, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2000952
关键词
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资金
- Israel Science Foundation
- Christopher and Dana Reeve Foundation
- International Institute for Research in Paraplegia
- Dr. Miriam and Sheldon Adelson Medical Research Foundation
- NIH [NCRR P41RR001614, NCRR RR012961]
- European Molecular Biology Organization
- Chaya Professorial Chair in Molecular Neuroscience
Retrograde signaling from axon to soma activates intrinsic regeneration mechanisms in lesioned peripheral sensory neurons; however, the links between axonal injury signaling and the cell body response are not well understood. Here, we used phosphoproteomics and microarrays to implicate similar to 900 phosphoproteins in retrograde injury signaling in rat sciatic nerve axons in vivo and similar to 4500 transcripts in the in vivo response to injury in the dorsal root ganglia. Computational analyses of these data sets identified similar to 400 redundant axonal signaling networks connected to 39 transcription factors implicated in the sensory neuron response to axonal injury. Experimental perturbation of individual overrepresented signaling hub proteins, including Abl, AKT, p38, and protein kinase C, affected neurite outgrowth in sensory neurons. Paradoxically, however, combined perturbation of Abl together with other hub proteins had a reduced effect relative to perturbation of individual proteins. Our data indicate that nerve injury responses are controlled by multiple regulatory components, and suggest that network redundancies provide robustness to the injury response.
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