GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout.

ABSTRACT: 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 dec

SUBMITTER: Leibinger M 

PROVIDER: S-EPMC6707209 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature