Premium
GSK3/CRMP2 signaling confers PTEN knockout mediated axonal regeneration
Author(s) -
Fischer Dietmar
Publication year - 2019
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2019.8244
Subject(s) - tensin , pten , regeneration (biology) , pi3k/akt/mtor pathway , axon , neurite , microbiology and biotechnology , biology , neuroscience , phosphatase , neuroprotection , knockout mouse , signal transduction , phosphorylation , receptor , genetics , in vitro
Knockout of phosphatase and tensin homolog (PTEN ‐/‐ ) is neuroprotective and promotes axon regeneration in mature neurons. Elevation and maintenance of mTOR activity in injured neurons have been proposed as the main 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