nArgBP2-SAPAP-SHANK, the core postsynaptic triad associated with psychiatric disorders

• Published in: Experimental & molecular medicine Vol. 50; no. 4; pp. 1 - 9
• Main Authors: Lee, Sang-Eun, Kim, Jung Ah, Chang, Sunghoe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.04.2018; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 692/699/375; 692/699/476; Actin; Adaptor Proteins, Signal Transducing; Animals; Behavior disorders; Biomedical and Life Sciences; Biomedicine; Cytoskeleton; Dendritic spines; Dendritic Spines - metabolism; Etiology; Homeodomain Proteins - metabolism; Humans; Medical Biochemistry; Mental disorders; Mental Disorders - etiology; Mental Disorders - metabolism; Mental Disorders - psychology; Models, Molecular; Molecular Medicine; Molecular modelling; Nerve Tissue Proteins - metabolism; Protein Binding; Proteins; Review; Review Article; RNA-Binding Proteins; SAP90-PSD95 Associated Proteins - metabolism; Stem Cells; Synapses; Synapses - metabolism; 생화학
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.1038/s12276-017-0018-5

Despite the complex genetic architecture, a broad spectrum of psychiatric disorders can still be caused by mutation(s) in the same gene. These disorders are interrelated with overlapping causative mechanisms including variations in the interaction among the risk-associated proteins that may give rise to the specific spectrum of each disorder. Additionally, multiple lines of evidence implicate an imbalance between excitatory and inhibitory neuronal activity (E/I imbalance) as the shared key etiology. Thus, understanding the molecular mechanisms underlying E/I imbalance provides essential insight into the etiology of these disorders. One important class of candidate risk genes is the postsynaptic scaffolding proteins, such as nArgBP2, SAPAP, and SHANK that regulate the actin cytoskeleton in dendritic spines of excitatory synapses. This review will cover and discuss recent studies that examined how these proteins, especially nArgBP2, are associated with psychiatric disorders. Next, we propose a possibility that variations in the interaction among these proteins in a specific brain region might contribute to the onset of diverse phenotypes of psychiatric disorders. Psychiatric disorder: Interactions between post-synaptic proteins The assembly of scaffolding proteins, key regulators of many signaling pathways, found in the brain’s synapses underpin a diverse range of neuropsychiatric disorders. Sunghoe Chang and colleagues from Seoul National University, South Korea, review how these postsynaptic proteins regulate the cellular cytoskeleton in nerve cell protrusions to maintain the balance between excitatory and inhibitory inputs in the brain. They discuss how perturbations in three particular proteins can cause an imbalance in synaptic signals that leads to conditions such as bipolar disorder, schizophrenia and autism. The authors propose that these proteins form a “core scaffolding triad” and interact in different ways to cause different mental illnesses. Dysregulation of these proteins could explain how mutations in the same genes, depending on whether they boost or decrease gene expression, contribute to the onset of diverse psychiatric disorders.