IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders

Abstract

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 filo-podia 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.