title: Tubulin-tyrosine Ligase (TTL)-mediated Increase in Tyrosinated α-Tubulin in Injured Axons Is Required for Retrograde Injury Signaling and Axon Regeneration.
abstract: Injured peripheral neurons successfully activate a pro-regenerative program to enable axon regeneration and functional recovery. The microtubule-dependent retrograde transport of injury signals from the lesion site in the axon back to the cell soma stimulates the increased growth capacity of injured neurons. However, the mechanisms initiating this retrograde transport remain poorly understood. Here we show that tubulin-tyrosine ligase (TTL) is required to increase the levels of tyrosinated α-tubulin at the axon injury site and plays an important role in injury signaling. Preventing the injury-induced increase in tyrosinated α-tubulin by knocking down TTL impairs retrograde organelle transport and delays activation of the pro-regenerative transcription factor c-Jun. In the absence of TTL, axon regeneration is reduced severely. We propose a model in which TTL increases the levels of tyrosinated α-tubulin locally at the injury site to facilitate the retrograde transport of injury signals that are required to activate a pro-regenerative program.
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Song
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Yongcheol
authors.initials: Y
authors.lastname: Cho
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110.
authors.forename: Dana
authors.initials: D
authors.lastname: Watt
authors.affiliation: From the Department of Anatomy and Neurobiology, Washington University in St. Louis, School of Medicine, St. Louis, Missouri 63110 cavalli@pcg.wustl.edu.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009416:Nerve Regeneration; D010453:Peptide Synthases / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000473:pathology / Q000502:physiology*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000032:analysis / Q000378:metabolism
chemical_list: D014404:Tubulin; D014443:Tyrosine; D010453:Peptide Synthases; C023213:tyrosyltubulin ligase
keywords: axon, regeneration, tubulin, tyrosinated tubulin, TTL, injury, signaling