Invited reviewIRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders

- IRSp53 is a scaffold/adaptor that regulates membrane/actin dynamics.
- IRSp53 regulates dendritic spine development and NMDAR function.
- IRSp53 is implicated in ASDs, schizophrenia, and ADHD.
- IRSp53−/− mice display NMDAR hyperfunction and social and cognitive deficits.
- NMDAR suppression rescues social and cognitive deficits in IRSp53−/− mice.

IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N-methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction.This article is part of the Special Issue entitled 'Synaptopathy - from Biology to Therapy'.