Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration

Neuron. 2012 Jun 21;74(6):1015-22. doi: 10.1016/j.neuron.2012.04.028.

Abstract

Here we demonstrate that the dual leucine zipper kinase (DLK) promotes robust regeneration of peripheral axons after nerve injury in mice. Peripheral axon regeneration is accelerated by prior injury; however, DLK KO neurons do not respond to a preconditioning lesion with enhanced regeneration in vivo or in vitro. Assays for activation of transcription factors in injury-induced proregenerative pathways reveal that loss of DLK abolishes upregulation of p-STAT3 and p-cJun in the cell body after axonal injury. DLK is not required for the phosphorylation of STAT3 at the site of nerve injury but is necessary for retrograde transport of p-STAT3 to the cell body. These data demonstrate that DLK enhances regeneration by promoting a retrograde injury signal that is required for the activation of the neuronal proregenerative program.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport / physiology*
  • Axons / metabolism
  • Axons / physiology*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • Mice, Knockout
  • Motor Neurons / metabolism
  • Motor Neurons / physiology*
  • Nerve Regeneration / physiology*
  • Peripheral Nerve Injuries / metabolism*
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism
  • Signal Transduction / physiology*
  • Up-Regulation / physiology

Substances

  • STAT3 Transcription Factor
  • MAP Kinase Kinase Kinases
  • mitogen-activated protein kinase kinase kinase 12