1. IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders
- Author
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Haram Park, Jaeseung Kang, and Eunjoon Kim
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Dendritic spine ,Dendritic Spines ,Nerve Tissue Proteins ,Biology ,Receptors, N-Methyl-D-Aspartate ,03 medical and health sciences ,Mice ,Cellular and Molecular Neuroscience ,medicine ,Animals ,Humans ,Protein Interaction Domains and Motifs ,RNA, Messenger ,Psychiatry ,Actin ,IRSp53 ,Pharmacology ,Mental Disorders ,Cell Membrane ,Membrane ,Brain ,Post-Synaptic Density ,medicine.disease ,Actin cytoskeleton ,NMDA receptor ,Cell biology ,Actin Cytoskeleton ,030104 developmental biology ,Phenotype ,Schizophrenia ,Excitatory postsynaptic potential ,Lamellipodium ,Psychiatric disorders ,Filopodia ,Postsynaptic density ,Neuroscience - 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 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’.
- Published
- 2016
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