Injury-induced HDAC5 nuclear export is essential for axon regeneration

Cell. 2013 Nov 7;155(4):894-908. doi: 10.1016/j.cell.2013.10.004.


Reactivation of a silent transcriptional program is a critical step in successful axon regeneration following injury. Yet how such a program is unlocked after injury remains largely unexplored. We found that axon injury in peripheral sensory neurons elicits a back-propagating calcium wave that invades the soma and causes nuclear export of HDAC5 in a PKCμ-dependent manner. Injury-induced HDAC5 nuclear export enhances histone acetylation to activate a proregenerative gene-expression program. HDAC5 nuclear export is required for axon regeneration, as expression of a nuclear-trapped HDAC5 mutant prevents axon regeneration, whereas enhancing HDAC5 nuclear export promotes axon regeneration in vitro and in vivo. Components of this HDAC5 pathway failed to be activated in a model of central nervous system injury. These studies reveal a signaling mechanism from the axon injury site to the soma that controls neuronal growth competence and suggest a role for HDAC5 as a transcriptional switch controlling axon regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus*
  • Animals
  • Axons / physiology*
  • Calcium Signaling
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Mice
  • Mutation
  • Nerve Regeneration
  • Sensory Receptor Cells / physiology*
  • Signal Transduction
  • Transcription, Genetic*


  • Hdac5 protein, mouse
  • Histone Deacetylases