TY - JOUR TI - An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK AU - Hao, Yan AU - Frey, Erin AU - Yoon, Choya AU - Wong, Hetty AU - Nestorovski, Douglas AU - Holzman, Lawrence B AU - Giger, Roman J AU - DiAntonio, Aaron AU - Collins, Catherine A2 - Bellen, Hugo J VL - 5 PY - 2016 DA - 2016/06/07 SP - e14048 C1 - eLife 2016;5:e14048 DO - 10.7554/eLife.14048 UR - https://doi.org/10.7554/eLife.14048 AB - 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. KW - axonal regeneration KW - cAMP signaiing KW - MAP Kinasae signaling JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -