Microtubule deacetylation sets the stage for successful axon regeneration.

Successful axon regeneration relies on a sophisticated balance between stable and dynamic microtubules. While it has been established that moderate microtubule stabilization improves regenerative performance, little is known how microtubules are normally regulated during regeneration. A new study by Cho and Cavalli (2012) uncovers an early role for local microtubule deacetylation that seems important for converting a cut axon stump to a regenerating axon. The authors demonstrate that histone deacetylase 5 is responsible for local deacetylation, and that it is locally activated by PKC downstream of axotomy-induced calcium influx. Axons in the peripheral nervous system (PNS) possess a robust ability to regrow after axotomy, whereas regeneration frequently fails in the central nervous system (CNS). Figuring out why PNS neurons regenerate so much better than CNS neurons may suggest strategies to improve CNS regeneration. Two key types of differences seem to be important: (1) a growth inhibitory environment in the CNS, and (2) a low intrinsic capacity to make a new axon in CNS neurons (Liu et al, 2011). Cho and Cavalli (2012) focus on a relatively uncharacterized aspect of the intrinsic growth response. For sustained axon regrowth, an injury signal needs to be sent back to the cell body and converted to a transcriptional response (Abe and Cavalli, 2008; Rishal and Fainzilber, 2010). However, before this happens, successful regeneration is presaged by specific local responses at the cut axon tip (Bradke et al, 2012). Shortly after axotomy, peripheral axon tips transform into growth cones consisting of organized microtubule bundles. In contrast, injured central axons swell into retraction bulbs enriched with destabilized microtubules (Erturk et al, 2007). Moreover, moderate microtubule stabilization helps CNS axons regenerate (Hellal et al, 2011). These results suggest that local control