Abstract
Axon degeneration underlies many common neurological disorders, but the signaling pathways that orchestrate axon degeneration are unknown. We found that dual leucine kinase (DLK) 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.
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Change history
15 May 2009
In the version of this article initially published, the abbreviation DLK was omitted from the abstract. The second sentence of the abstract should be “We found that dual leucine kinase (DLK) 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.” The error has been corrected in the HTML and PDF versions of the article.
References
Saxena, S. & Caroni, P. Prog. Neurobiol. 83, 174–191 (2007).
Coleman, M. Nat. Rev. Neurosci. 6, 889–898 (2005).
Mack, T.G. et al. Nat. Neurosci. 4, 1199–1206 (2001).
Araki, T., Sasaki, Y. & Milbrandt, J. Science 305, 1010–1013 (2004).
Wang, J. et al. J. Cell Biol. 170, 349–355 (2005).
George, E.B., Glass, J.D. & Griffin, J.W. J. Neurosci. 15, 6445–6452 (1995).
Zhai, Q. et al. Neuron 39, 217–225 (2003).
MacDonald, J.M. et al. Neuron 50, 869–881 (2006).
Luo, L. & O'Leary, D.D. Annu. Rev. Neurosci. 28, 127–156 (2005).
Gallo, K.A. & Johnson, G.L. Nat. Rev. Mol. Cell Biol. 3, 663–672 (2002).
Cavalli, V., Kujala, P., Klumperman, J. & Goldstein, L.S. J. Cell Biol. 168, 775–787 (2005).
Hoopfer, E.D. et al. Neuron 50, 883–895 (2006).
Collins, C.A., Wairkar, Y.P., Johnson, S.L. & DiAntonio, A. Neuron 51, 57–69 (2006).
Bloom, A.J., Miller, B.R., Sanes, J.R. & DiAntonio, A. Genes Dev. 21, 2593–2606 (2007).
Wang, M.S., Wu, Y., Culver, D.G. & Glass, J.D. J. Neuropathol. Exp. Neurol. 59, 599–606 (2000).
Acknowledgements
We thank the members of our laboratories, V. Cavalli and E.M. Johnson. This work was supported by US National Institutes of Health grants P30 NS057105 to Washington University, NS040745 (J.M.), AG13730 (J.M.), DA 020812 (A.D.), Washington University Alzheimer's Disease Research Center National Institute on Aging grant NIA P50 AG05681-25 (A.D.), the Hope Center for Neurological Disorders and the Keck Foundation (A.D.).
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B.R.M. designed and conducted all of the experiments and co-wrote the manuscript. C.P. helped to design and to conduct the in vitro DRG experiments. R.W.D. contributed to the electron microscopy analysis. Y.S. developed the degeneration index algorithm. J.M. helped to supervise the project. A.D. supervised the project and co-wrote the manuscript.
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Miller, B., Press, C., Daniels, R. et al. A dual leucine kinase–dependent axon self-destruction program promotes Wallerian degeneration. Nat Neurosci 12, 387–389 (2009). https://doi.org/10.1038/nn.2290
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DOI: https://doi.org/10.1038/nn.2290
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