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An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK

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Title: An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK
Authors: Yan Hao, Erin Frey, Choya Yoon, Hetty Wong, Douglas Nestorovski, Lawrence B Holzman, Roman J Giger, Aaron DiAntonio, Catherine Collins
Source: eLife, Vol 5 (2016)
Publisher Information: eLife Sciences Publications Ltd, 2016.
Publication Year: 2016
Collection: LCC:Medicine
LCC:Science
LCC:Biology (General)
Subject Terms: axonal regeneration, cAMP signaiing, MAP Kinasae signaling, Medicine, Science, Biology (General), QH301-705.5
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2050-084X
Relation: https://elifesciences.org/articles/14048; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.14048
Access URL: https://doaj.org/article/ac9221f744814f329a98443715a0432f
Accession Number: edsdoj.9221f744814f329a98443715a0432f
Database: Directory of Open Access Journals
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  Data: An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK
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  Data: <searchLink fieldCode="AR" term="%22Yan+Hao%22">Yan Hao</searchLink><br /><searchLink fieldCode="AR" term="%22Erin+Frey%22">Erin Frey</searchLink><br /><searchLink fieldCode="AR" term="%22Choya+Yoon%22">Choya Yoon</searchLink><br /><searchLink fieldCode="AR" term="%22Hetty+Wong%22">Hetty Wong</searchLink><br /><searchLink fieldCode="AR" term="%22Douglas+Nestorovski%22">Douglas Nestorovski</searchLink><br /><searchLink fieldCode="AR" term="%22Lawrence+B+Holzman%22">Lawrence B Holzman</searchLink><br /><searchLink fieldCode="AR" term="%22Roman+J+Giger%22">Roman J Giger</searchLink><br /><searchLink fieldCode="AR" term="%22Aaron+DiAntonio%22">Aaron DiAntonio</searchLink><br /><searchLink fieldCode="AR" term="%22Catherine+Collins%22">Catherine Collins</searchLink>
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  Data: eLife, Vol 5 (2016)
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  Data: eLife Sciences Publications Ltd, 2016.
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  Data: 2016
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  Data: LCC:Medicine<br />LCC:Science<br />LCC:Biology (General)
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  Data: <searchLink fieldCode="DE" term="%22axonal+regeneration%22">axonal regeneration</searchLink><br /><searchLink fieldCode="DE" term="%22cAMP+signaiing%22">cAMP signaiing</searchLink><br /><searchLink fieldCode="DE" term="%22MAP+Kinasae+signaling%22">MAP Kinasae signaling</searchLink><br /><searchLink fieldCode="DE" term="%22Medicine%22">Medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Science%22">Science</searchLink><br /><searchLink fieldCode="DE" term="%22Biology+%28General%29%22">Biology (General)</searchLink><br /><searchLink fieldCode="DE" term="%22QH301-705%2E5%22">QH301-705.5</searchLink>
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  Label: Description
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  Data: 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.
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  Data: https://elifesciences.org/articles/14048; https://doaj.org/toc/2050-084X
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  Data: 10.7554/eLife.14048
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        Value: 10.7554/eLife.14048
    Languages:
      – Text: English
    Subjects:
      – SubjectFull: axonal regeneration
        Type: general
      – SubjectFull: cAMP signaiing
        Type: general
      – SubjectFull: MAP Kinasae signaling
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      – SubjectFull: Medicine
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      – TitleFull: An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK
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