IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders.
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'.
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea.
Jaeseung
J
Kang
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea.
Haram
H
Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea; Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 305-701, South Korea. Electronic address: kime@kaist.ac.kr.
Eunjoon
E
Kim
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D057907:Post-Synaptic Density / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
C119539:BAIAP2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins
Actin; Dendritic spine; IRSp53; Membrane; NMDA receptor; Psychiatric disorders