Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration

Bo Yin Zhang, Saijilafu, Chang Mei Liu, Rui Ying Wang, Qingsan Zhu, Zhongxian Jiao, Feng Quan Zhou

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Inactivation of glycogen synthase kinase 3 (GSK3) has been shown to mediate axon growth during development and regeneration. Phosphorylation of GSK3 by the kinase Akt is well known to be the major mechanism by which GSK3 is inactivated. However, whether such regulatory mechanism of GSK3 inactivation is used in neurons to control axon growth has not been directly studied. Here by using GSK3 mutant mice, in which GSK3 is insensitive to Akt-mediated inactivation, we show that sensory axons regenerate normally in vitro and in vivo after peripheral axotomy. We also find that GSK3 in sensory neurons of the mutant mice is still inactivated in response to peripheral axotomy and such inactivation is required for sensory axon regeneration. Lastly, we provide evidence that GSK3 activity is negatively regulated by PI3K signaling in the mutant mice upon peripheral axotomy, and the PI3K-GSK3 pathway is functionally required for sensory axon regeneration. Together, these results indicate that in response to peripheral nerve injury GSK3 inactivation, regulated by an alternative mechanism independent of Akt-mediated phosphorylation, controls sensory axon regeneration.

Original languageEnglish (US)
Pages (from-to)743-748
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Jan 10 2014
Externally publishedYes


  • Axon regeneration
  • GSK3 signaling
  • In vivo electroporation
  • PI3K signaling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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