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

SummaryThe 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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (343 K)Download as PowerPoint slideHighlights► Axon injury triggers a two-phase process of microtubule (MT) growth upregulation ► The depolymerizing kinesin-13 KLP-7 is locally downregulated at the axon stump ► Tubulin posttranslational modifications regulate axon regeneration ► The DLK-1 pathway regulates both axonal kinesin-13 and tubulin modifications