XInjury-Induced HDAC5 nuclear export is essential for axon regeneration

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

Research output: Contribution to journalArticle

148 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
Number of pages1
JournalCell
Volume155
Issue number4
DOIs
Publication statusPublished - 2013 Nov 7
Externally publishedYes

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Cell Nucleus Active Transport
Axons
Regeneration
Wounds and Injuries
Carisoprodol
Nervous System Trauma
Acetylation
Calcium Signaling
Neurology
Sensory Receptor Cells
Gene expression
Histones
Mental Competency
Neurons
Central Nervous System
Switches
Calcium
Gene Expression
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

XInjury-Induced HDAC5 nuclear export is essential for axon regeneration. / Cho, Yongcheol; Sloutsky, Roman; Naegle, Kristen M.; Cavalli, Valeria.

In: Cell, Vol. 155, No. 4, 07.11.2013.

Research output: Contribution to journalArticle

Cho, Yongcheol ; Sloutsky, Roman ; Naegle, Kristen M. ; Cavalli, Valeria. / XInjury-Induced HDAC5 nuclear export is essential for axon regeneration. In: Cell. 2013 ; Vol. 155, No. 4.
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