An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK
| 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 |
| ISSN: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.14048 |
| Published in: | eLife |
| Language: | English |