XInjury-Induced HDAC5 nuclear export is essential for axon regeneration

Yongcheol Cho, Roman Sloutsky, Kristen M. Naegle, Valeria Cavalli

Research output: Contribution to journalArticlepeer-review

167 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)894
Number of pages1
JournalCell
Volume155
Issue number4
DOIs
Publication statusPublished - 2013 Nov 7

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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