Modifying PTEN recruitment promotes neuron survival, regeneration, and functional recovery after CNS injury.

Phosphatase and tensin homolog (PTEN) regulates apoptosis and axonal growth in the developing and adult central nervous system (CNS). Here, we show that human PTEN C-terminal PDZ interactions play a critical role in neuronal apoptosis and axon regeneration after traumatic CNS injury and stroke, highlighted by the findings that antagonizing the PDZ-motif interactions of PTEN has therapeutic applicability for these indications. Interestingly, the death-inducing function of PTEN following ischemic insult depends on a PDZ-domain interaction with MAGI-2 and MAST205, PDZ proteins that are known to recruit PTEN to the plasma membrane and stabilize its interaction with PIP3.