GSK3 beta regulates AKT-induced central nervous system axon regeneration via an eIF2B epsilon-dependent mTORC1-independent pathway

作者：Guo Xinzheng; Snider William D; Chen Bo^*

来源：eLife, 2016, 5: e11903.

DOI：10.7554/eLife.11903

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 GSK3 beta plays an indispensable role in mediating AKT-induced axon regeneration. Deletion or inactivation of GSK3 beta promotes axon regeneration independently of the mTORC1 pathway, whereas constitutive activation of GSK3 beta reduces AKT-induced axon regeneration. Importantly, we have identified eIF2B epsilon as a novel downstream effector of GSK3 beta in regulating axon regeneration. Inactivation of eIF2B epsilon reduces both GSK3 beta and AKT-mediated effects on axon regeneration. Constitutive activation of eIF2B epsilon is sufficient to promote axon regeneration. Our results reveal a key role of the AKT-GSK3 beta-eIF2B epsilon signaling module in regulating axon regeneration in the adult mammalian CNS.

• 出版日期2016-3-14