| First Author | Guo X | Year | 2016 |
| Journal | Elife | Volume | 5 |
| Pages | e11903 | PubMed ID | 26974342 |
| Mgi Jnum | J:231148 | Mgi Id | MGI:5767014 |
| Doi | 10.7554/eLife.11903 | Citation | Guo X, et al. (2016) GSK3beta regulates AKT-induced central nervous system axon regeneration via an eIF2Bepsilon-dependent, mTORC1-independent pathway. Elife 5:e11903 |
| abstractText | 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 GSK3beta plays an indispensable role in mediating AKT-induced axon regeneration. Deletion or inactivation of GSK3beta promotes axon regeneration independently of the mTORC1 pathway, whereas constitutive activation of GSK3beta reduces AKT-induced axon regeneration. Importantly, we have identified eIF2Bepsilon as a novel downstream effector of GSK3beta in regulating axon regeneration. Inactivation of eIF2Bepsilon reduces both GSK3beta and AKT-mediated effects on axon regeneration. Constitutive activation of eIF2Bepsilon is sufficient to promote axon regeneration. Our results reveal a key role of the AKT-GSK3beta-eIF2Bepsilon signaling module in regulating axon regeneration in the adult mammalian CNS. |
