Citation

Cho Y, Cavalli V. EMBO J. 2012; 31(14): 3063-3078.

Affiliation

Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA.

Copyright

(Copyright © 2012, European Molecular Biology Organization, Publisher Nature Publishing Group)

DOI

10.1038/emboj.2012.160

PMID

22692128

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.

Language: en