title: Filamin A is required in injured axons for HDAC5 activity and axon regeneration.
abstract: Microtubule dynamics are important for axon growth during development as well as axon regeneration after injury. We have previously identified HDAC5 as an injury-regulated tubulin deacetylase that functions at the injury site to promote axon regeneration. However, the mechanisms involved in the spatial control of HDAC5 activity remain poorly understood. Here we reveal that HDAC5 interacts with the actin binding protein filamin A via its C-terminal domain. Filamin A plays critical roles in HDAC5-dependent tubulin deacetylation because, in cells lacking filamin A, the levels of acetylated tubulin are elevated markedly. We found that nerve injury increases filamin A axonal expression in a protein synthesis-dependent manner. Reducing filamin A levels or interfering with the interaction between HDAC5 and filamin A prevents injury-induced tubulin deacetylation as well as HDAC5 localization at the injured axon tips. In addition, neurons lacking filamin A display reduced axon regeneration. Our findings suggest a model in which filamin A local translation following axon injury controls localized HDAC5 activity to promote axon regeneration.
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110 and.
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Cho
authors.affiliation: the School of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea depark@snu.ac.kr.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110 and cavalli@pcg.wustl.edu.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
mesh_terms: D000107:Acetylation; D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D064448:Filamins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D021381:Protein Transport / Q000235:genetics; D012038:Regeneration; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D064448:Filamins; D014404:Tubulin; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
keywords: axon; deacetylation; filamin; histone deacetylase (HDAC); regeneration; tubulin