Filamin a is required in injured axons for HDAC5 activity and axon regeneration

Yongcheol Cho, Dongeun Park, Valeria Cavalli

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Microtubule dynamics are important for axon growth during development as well as axon regeneration after injury. We have previously identified HDAC5 as an injury-regulated tubulin deacetylase that functions at the injury site to promote axon regeneration. However, the mechanisms involved in the spatial control of HDAC5 activity remain poorly understood. Here we reveal that HDAC5 interacts with the actin binding protein filamin A via its C-terminal domain. Filamin A plays critical roles in HDAC5-dependent tubulin deacetylation because, in cells lacking filamin A, the levels of acetylated tubulin are elevated markedly. We found that nerve injury increases filamin A axonal expression in a protein synthesis-dependent manner. Reducing filamin A levels or interfering with the interaction between HDAC5 and filaminAprevents injury-induced tubulin deacetylation as well as HDAC5 localization at the injured axon tips. In addition, neurons lacking filamin A display reduced axon regeneration. Our findings suggest a model in which filaminAlocal translation following axon injury controls localized HDAC5 activity to promote axon regeneration.

Original languageEnglish
Pages (from-to)22759-22770
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number37
DOIs
Publication statusPublished - 2015 Sep 11
Externally publishedYes

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Filamins
Axons
Regeneration
Tubulin
Wounds and Injuries
Microfilament Proteins
Growth and Development
Microtubules
Neurons
Display devices

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Filamin a is required in injured axons for HDAC5 activity and axon regeneration. / Cho, Yongcheol; Park, Dongeun; Cavalli, Valeria.

In: Journal of Biological Chemistry, Vol. 290, No. 37, 11.09.2015, p. 22759-22770.

Research output: Contribution to journalArticle

Cho, Yongcheol ; Park, Dongeun ; Cavalli, Valeria. / Filamin a is required in injured axons for HDAC5 activity and axon regeneration. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 37. pp. 22759-22770.
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