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Citation
Hao, Y., Frey, E., Yoon, C., Wong, H., Nestorovski, D., Holzman, L.B., Giger, R.J., DiAntonio, A., Collins, C. (2016). An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK.  eLife 5(): e14048.
FlyBase ID
FBrf0232627
Publication Type
Research paper
Abstract

A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons.

PubMed ID
PubMed Central ID
PMC4896747 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    eLife
    Title
    eLife
    ISBN/ISSN
    2050-084X
    Data From Reference