Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration.
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.
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jung Eun
JE
Shin
Yongcheol
Y
Cho
Bogdan
B
Beirowski
Jeffrey
J
Milbrandt
Valeria
V
Cavalli
Aaron
A
DiAntonio
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D050796:STAT3 Transcription Factor; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12