HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration

Yongcheol Cho, Valeria Cavalli

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Axon regeneration is an essential process to rebuild functional connections between injured neurons and their targets. Regenerative axonal growth requires alterations in axonal microtubule dynamics, but the signalling mechanisms involved remain incompletely understood. Our results reveal that axon injury induces a gradient of tubulin deacetylation, which is required for axon regeneration both in vitro and in vivo. This injury-induced tubulin deacetylation is specific to peripheral neurons and fails to occur in central neurons. We found that tubulin deacetylation is initiated by calcium influx at the site of injury, and requires protein kinase C-mediated activation of the histone deacetylase 5 (HDAC5). Our findings identify HDAC5 as a novel injury-regulated tubulin deacetylase that plays an essential role in growth cone dynamics and axon regeneration. In addition, our results suggest a mechanism for the spatial control of tubulin modifications that is required for axon regeneration.

Original languageEnglish
Pages (from-to)3063-3078
Number of pages16
JournalEMBO Journal
Volume31
Issue number14
DOIs
Publication statusPublished - 2012 Jul 18
Externally publishedYes

Fingerprint

Histone Deacetylases
Tubulin
Axons
Regeneration
Wounds and Injuries
Neurons
Growth Cones
Microtubules
Protein Kinase C
Cones
Chemical activation
Calcium
Growth

Keywords

  • axon regeneration
  • calcium signalling
  • histone deacetylase
  • microtubule
  • protein kinase C

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

HDAC5 is a novel injury-regulated tubulin deacetylase controlling axon regeneration. / Cho, Yongcheol; Cavalli, Valeria.

In: EMBO Journal, Vol. 31, No. 14, 18.07.2012, p. 3063-3078.

Research output: Contribution to journalArticle

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