Dual Leucine Zipper Kinase Is Required for Retrograde Injury Signaling and Axonal Regeneration

作者：Shin Jung Eun; Cho Yongcheol; Beirowski Bogdan; Milbrandt Jeffrey; Cavalli Valeria; DiAntonio Aaron^*

来源：Neuron, 2012, 74(6): 1015-1022.

DOI：10.1016/j.neuron.2012.04.028

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.

• 出版日期2012-6-21