PTEN: A master regulator of neuronal structure, function, and plasticity

Abstract

PTEN (phosphatase and tensin homolog on chromosome ten) is a dual protein/lipid phosphatase that dephosphorylates PIP3, thereby inhibiting the AKT/mTOR pathway. This inhibition ultimately decreases protein translation, cell proliferation and cell growth. In the central nervous system, inhibition of PTEN leads to increased stem cell proliferation, somatic, dendritic and axonal growth, accelerated spine maturation, diminished synaptic plasticity, and altered intrinsic excitability. In agreement with these findings, patients carrying single-copy inactivating mutations of PTEN suffer from autism, macrocephaly, mental retardation, and epilepsy.(1) (-) (9) Understanding the mechanisms through which PTEN modulates the structure, function, and plasticity of cortical networks is a major focus of study. Preventing and reversing the changes induced by loss of Pten in model animals will pave the way for treatments in humans.

Keywords: LTP; PTEN; autism; cortex; development; epilepsy; hippocampus; mTOR; plasticity.

Figure 1. (A) Left: A drawing representing dendritic and axonal growth caused by loss of PTEN. Insets: PTEN loss causes increased synaptic vesicles and dendritic protrusions. Right: List of changes in neuronal anatomy caused by loss of PTEN. The numbers are references supporting each finding. (B) An illustration demonstrating the potential role of PTEN in synaptic long-term depression (LTD) and long term potentiation (LTP). C. A schematic illustrating that loss of PTEN leads to increased expression of calcium-activated potassium channels and decreased intrinsic excitability which is in turn rescued by treatment with the SK channel blocker, apamin.