TY - JOUR TI - GSK3β regulates AKT-induced central nervous system axon regeneration via an eIF2Bε-dependent, mTORC1-independent pathway AU - Guo, Xinzheng AU - Snider, William D AU - Chen, Bo A2 - Sonenberg, Nahum VL - 5 PY - 2016 DA - 2016/03/14 SP - e11903 C1 - eLife 2016;5:e11903 DO - 10.7554/eLife.11903 UR - https://doi.org/10.7554/eLife.11903 AB - Axons fail to regenerate after central nervous system (CNS) injury. Modulation of the PTEN/mTORC1 pathway in retinal ganglion cells (RGCs) promotes axon regeneration after optic nerve injury. Here, we report that AKT activation, downstream of Pten deletion, promotes axon regeneration and RGC survival. We further demonstrate that GSK3β plays an indispensable role in mediating AKT-induced axon regeneration. Deletion or inactivation of GSK3β promotes axon regeneration independently of the mTORC1 pathway, whereas constitutive activation of GSK3β reduces AKT-induced axon regeneration. Importantly, we have identified eIF2Bε as a novel downstream effector of GSK3β in regulating axon regeneration. Inactivation of eIF2Bε reduces both GSK3β and AKT-mediated effects on axon regeneration. Constitutive activation of eIF2Bε is sufficient to promote axon regeneration. Our results reveal a key role of the AKT-GSK3β-eIF2Bε signaling module in regulating axon regeneration in the adult mammalian CNS. KW - CNS axon regeneration KW - axon injury KW - signal transduction JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -