期刊
CELL
卷 155, 期 4, 页码 894-908出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.10.004
关键词
-
资金
- NIH [DE022000, NS082446]
- McDonnell Center for Cellular and Molecular Neurobiology
- Hope Center for Neurological Disorders
- National Research Foundation of Korea [NRF-2012R1A6A3A03039290]
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 PKC mu-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.
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