Kinesin-13 and Tubulin Posttranslational Modifications Regulate Microtubule Growth in Axon Regeneration

摘要

The microtubule (MT) cytoskeleton of a mature axon is maintained in a stabilized steady state, yet after axonal injury it can be transformed into a dynamic structure capable of supporting axon regrowth. Using Caenorhabditis elegans mechanosensory axons and in vivo imaging, we find that, in mature axons, the growth of MTs is restricted in the steady state by the depolymerizing kinesin-13 family member KLP-7. After axon injury, we observe a two-phase process of MT growth upregulation. First, the number of growing MTs increases at the injury site, concomitant with local downregulation of KLP-7. A second phase of persistent MT growth requires the cytosolic carboxypeptidase CCPP-6, which promotes Δ2 modification of α-tubulin. Both phases of MT growth are coordinated by the DLK-1 MAP kinase cascade. Our results define how the stable MT cytoskeleton of a mature neuron is converted into the dynamically growing MT cytoskeleton of a regrowing axon. Axon regeneration after injury involves conversion of the stable microtubule (MT) cytoskeleton of a mature axon into the dynamic cytoskeleton of a regrowing process. Using C. elegans in vivo imaging, Ghosh-Roy et al. show that the DLK-1 pathway regulates this transition via an MT depolymerizing kinesin and tubulin posttranslational modifications.