The Role of PTEN in Neurodevelopment

Abstract

PTEN is a lipid and protein phosphatase that regulates cell growth and survival. Mutations to PTEN are highly penetrant for autism spectrum disorder (ASD). Here, we briefly review the evidence linking PTEN mutations to ASD and the mouse models that have been used to study the role of PTEN in neurodevelopment. We then focus on the cellular phenotypes associated with PTEN loss in neurons, highlighting the role PTEN plays in neuronal proliferation, migration, survival, morphology, and plasticity.

Keywords: ASD; Autism; Autism spectrum disorder; Epilepsy; PTEN; Synapse.

Fig. 1

Major structural features of PTEN. PTEN has an N-terminal PIP2-binding domain (PBD) and phosphatase domain (amino acids 7–185), containing the catalytic P-loop (123–130). A C2 domain (186–351) contains a CBR3 loop from 260–269, which mediates membrane binding. An unstructured C-terminal tail contains multiple phosphorylation sites which inhibit catalytic activity and membrane binding. The terminus of this tail contains a PDZ-binding motif (based on [33] and [58]).