| First Author | Leibinger M | Year | 2019 |
| Journal | Commun Biol | Volume | 2 |
| Pages | 318 | PubMed ID | 31453382 |
| Mgi Jnum | J:288939 | Mgi Id | MGI:6433528 |
| Doi | 10.1038/s42003-019-0524-1 | Citation | Leibinger M, et al. (2019) GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout. Commun Biol 2:318 |
| abstractText | Knockout of phosphatase and tensin homolog (PTEN(-/-)) is neuroprotective and promotes axon regeneration in mature neurons. Elevation of mTOR activity in injured neurons has been proposed as the primary underlying mechanism. Here we demonstrate that PTEN(-/-) also abrogates the inhibitory activity of GSK3 on collapsin response mediator protein 2 (CRMP2) in retinal ganglion cell (RGC) axons. Moreover, maintenance of GSK3 activity in Gsk3 (S/A) knockin mice significantly compromised PTEN(-/-)-mediated optic nerve regeneration as well as the activity of CRMP2, and to a lesser extent, mTOR. These GSK3(S/A) mediated negative effects on regeneration were rescued by viral expression of constitutively active CRMP2(T/A), despite decreased mTOR activation. Gsk3 (S/A) knockin or CRMP2 inhibition also decreased PTEN(-/-) mediated neurite growth of RGCs in culture and disinhibition towards CNS myelin. Thus, the GSK3/CRMP2 pathway is essential for PTEN(-/-) mediated axon regeneration. These new mechanistic insights may help to find novel strategies to promote axon regeneration. |
