A dual leucine kinase-dependent axon self-destruction program promotes Wallerian degeneration.
Axon degeneration underlies many common neurological disorders, but the signaling pathways that orchestrate axon degeneration are unknown. We found that dual leucine kinase (DLK) [corrected to add (DLK) abbreviation] promoted degeneration of severed axons in Drosophila and mice, and that its target, c-Jun N-terminal kinase, promoted degeneration locally in axons as they committed to degenerate. This pathway also promoted degeneration after chemotherapy exposure and may be a component of a general axon self-destruction program.
Miller
Bradley R
BR
Department of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.
Press
Craig
C
Daniels
Richard W
RW
Sasaki
Yo
Y
Milbrandt
Jeffrey
J
DiAntonio
Aaron
A
D000818:Animals; D030801:Animals, Genetically Modified; D000873:Anthracenes / Q000494:pharmacology; D001369:Axons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D019771:Axotomy / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004330:Drosophila; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018034:Olfactory Receptor Neurons / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology; D014855:Wallerian Degeneration / Q000235:genetics / Q000473:pathology*
D000873:Anthracenes; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12