Deciphering how PTEN phosphatase mediates excitotoxicneuronal death
Ischemic insults such as head injury and stroke induce excessive release of glutamate from the injured neurons into the extracellular space. The excess glutamate then induces death of the surrounding neurons by over-stimulating their glutamate receptors. Understanding the molecular basis of excitotoxic neuronal death is the best avenue to facilitate development of therapeutic agents. We discovered for the first time that glutamate receptor over-stimulation induces enhanced membrane localisation of PTEN and two types of modifications to PTEN's C-terminal tail:
- Dephosphorylation by unknown phosphatases
- Truncation by calpain
Presumably, both modifications relieve the inhibitory constraint of the C-terminal tail on PTEN activity and subcellular localisation. Our main objective is to decipher the mechanism by which PTEN is recruited by the over-stimulated glutamate receptor to enhance excitotoxic neuronal death.
- Associate Professor Steve Cheung (Research Fellow)
- Associate Professor Heung-Chin Cheng, University of Melbourne