Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Jun 2012
Disruption of E3 ligase NEDD4 in peripheral neurons interrupts axon outgrowth: Linkage to PTEN.
Exploiting molecules and pathways important in developmental axon behaviour may offer new insights into regenerative behaviour of adult peripheral neurons after injury. In previous work, we have provided evidence that inhibition or knockdown of PTEN (phosphatase and tensin homolog deleted on chromosome ten) dramatically increases adult peripheral axon outgrowth, especially in preconditioned neurons (Christie et al., 2010). PTEN appears to operate as an endogenous brake to regeneration. ⋯ A significant role for this unique co-expression was observed with fluorescently tagged siRNA inhibition of Nedd4, which decreased neurite outgrowth, an impact associated with greater expression of PTEN and that was completely reversed with application of a PTEN inhibitor. Overall, our results suggest an important role for Nedd4 regulation of PTEN in the response of peripheral neurons to injury. By degrading PTEN among other potential actions, Nedd4 supports axonal outgrowth whereas its inhibition facilitates PTEN inhibition of regeneration.