title: Injury-induced HDAC5 nuclear export is essential for axon regeneration.
abstract: 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.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Cho
authors.forename: Roman
authors.initials: R
authors.lastname: Sloutsky
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Naegle
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001369:Axons / Q000502:physiology*; D020013:Calcium Signaling; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009416:Nerve Regeneration; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases