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Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways

2011; National Academy of Sciences; Volume: 108; Issue: 26 Linguagem: Inglês

10.1073/pnas.1104830108

1091-6490

Paola Nix, Naoki Hisamoto, Kunihiro Matsumoto, Michael J. Bastiani,

Axon Guidance and Neuronal Signaling

Signaling pathways essential for axon regeneration, but not for neuron development or function, are particularly well suited targets for therapeutic intervention. We find that the parallel PMK-3(p38) and KGB-1(JNK) MAPK pathways must be coordinately activated to promote axon regeneration. Axon regeneration fails if the activity of either pathway is absent. These two MAPKs are coregulated by the E3 ubiquitin ligase RPM-1(Phr1) via targeted degradation of the MAPKKKs DLK-1 and MLK-1 and by the MAPK phosphatase VHP-1(MKP7), which negatively regulates both PMK-3(p38) and KGB-1(JNK).