biostudies-literature00480Cho YNIDCR NIH HHSNINDS NIH HHS894-908https://www.ebi.ac.uk/biostudies/studies/S-EPMC3987749biostudies-literatureUnknown155(4)Reactivation of a silent transcriptional program is a critical step in successful axon regeneration following injury. Yet how such a program is unlocked after injury remains largely unexplored. We found that axon injury in peripheral sensory neurons elicits a back-propagating calcium wave that invades the soma and causes nuclear export of HDAC5 in a PKCμ-dependent manner. Injury-induced HDAC5 nuclear export enhances histone acetylation to activate a proregenerative gene-expression program. HDAC5 nuclear export is required for axon regeneration, as expression of a nuclear-trapped HDAC5 mutant prevents axon regeneration, whereas enhancing HDAC5 nuclear export promotes axon regeneration in vitro and in vivo. Components of this HDAC5 pathway failed to be activated in a model of central nervous system injury. These studies reveal a signaling mechanism from the axon injury site to the soma that controls neuronal growth competence and suggest a role for HDAC5 as a transcriptional switch controlling axon regeneration.CellInjury-induced HDAC5 nuclear export is essential for axon regeneration.PMC3987749R01 NS082446NS082446R01 DE022000DE022000Naegle KMCho YCavalli VSloutsky R48falseInjury-induced HDAC5 nuclear export is essential for axon regeneration.Reactivation of a silent transcriptional program is a critical step in successful axon regeneration following injury. Yet how such a program is unlocked after injury remains largely unexplored. We found that axon injury in peripheral sensory neurons elicits a back-propagating calcium wave that invades the soma and causes nuclear export of HDAC5 in a PKCμ-dependent manner. Injury-induced HDAC5 nuclear export enhances histone acetylation to activate a proregenerative gene-expression program. HDAC5 nuclear export is required for axon regeneration, as expression of a nuclear-trapped HDAC5 mutant prevents axon regeneration, whereas enhancing HDAC5 nuclear export promotes axon regeneration in vitro and in vivo. Components of this HDAC5 pathway failed to be activated in a model of central nervous system injury. These studies reveal a signaling mechanism from the axon injury site to the soma that controls neuronal growth competence and suggest a role for HDAC5 as a transcriptional switch controlling axon regeneration.2013-01-01T00:00:00Z2013 Nov2024-11-06T22:31:05.736Z2019-03-27T01:25:08ZS-EPMC39877492420962610.1016/j.cell.2013.10.004