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

236 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
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Vitaly Klyachko for critical reading of the manuscript. We thank Eric Olson for the generous gift of the HDAC5 KO mice. We thank Domini Montgomery for technical support, Dennis Oakley for assistance with imaging, Ernie Gonzales and the Animal Surgery Core of the Hope Center for Neurological Disorders for assistance with optic nerve surgeries, and Seth Crosby and the Genome Technology Access Center at Washington University for microarray analysis. This work was supported in part by grants from NIH (DE022000 and NS082446), the McDonnell Center for Cellular and Molecular Neurobiology, the Hope Center for Neurological Disorders (to V.C.), and the National Research Foundation of Korea (NRF-2012R1A6A3A03039290) (to Y.C.).

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology

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