Tubulin-tyrosine ligase (TTL)-mediated increase in tyrosinated α-tubulin in injured axons is required for retrograde injury signaling and axon regeneration

Wenjun Song, Yongcheol Cho, Dana Watt, Valeria Cavalli

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14765-14775
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number23
DOIs
Publication statusPublished - 2015 Jun 5
Externally publishedYes

Fingerprint

Tubulin
Axons
Regeneration
Wounds and Injuries
Neurons
Carisoprodol
Transcription Factors
Chemical activation
Recovery
Microtubules
Organelles
tyrosyltubulin ligase
Growth

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tubulin-tyrosine ligase (TTL)-mediated increase in tyrosinated α-tubulin in injured axons is required for retrograde injury signaling and axon regeneration. / Song, Wenjun; Cho, Yongcheol; Watt, Dana; Cavalli, Valeria.

In: Journal of Biological Chemistry, Vol. 290, No. 23, 05.06.2015, p. 14765-14775.

Research output: Contribution to journalArticle

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