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 language | English |
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Pages (from-to) | 3063-3078 |
Number of pages | 16 |
Journal | EMBO Journal |
Volume | 31 |
Issue number | 14 |
DOIs | |
Publication status | Published - 2012 Jul 18 |
Externally published | Yes |
Keywords
- axon regeneration
- calcium signalling
- histone deacetylase
- microtubule
- protein kinase C
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- General Biochemistry,Genetics and Molecular Biology
- General Immunology and Microbiology