TY - JOUR
T1 - Tubulin-tyrosine ligase (TTL)-mediated increase in tyrosinated α-tubulin in injured axons is required for retrograde injury signaling and axon regeneration
AU - Song, Wenjun
AU - Cho, Yongcheol
AU - Watt, Dana
AU - Cavalli, Valeria
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/6/5
Y1 - 2015/6/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930651553&partnerID=8YFLogxK
U2 - 10.1074/jbc.M114.622753
DO - 10.1074/jbc.M114.622753
M3 - Article
C2 - 25911101
AN - SCOPUS:84930651553
SN - 0021-9258
VL - 290
SP - 14765
EP - 14775
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 23
ER -