title: nArgBP2 as a hub molecule in the etiology of various neuropsychiatric disorders.
abstract: Recent studies have strongly implicated postsynaptic scaffolding proteins such as SAPAP3 or Shank3 in the pathogenesis of various mood disorders, including autism spectrum disorder, bipolar disorder (BD), and obsessive-compulsive disorders. Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that interacts with SAPAP3 and Shank3. Recent study shows that the genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behavior resembling symptoms of BD. However, the function of nArgBP2 at synapse, or its connection with the synaptic dysfunctions, is completely unknown. This study provides compelling evidence that nArgBP2 regulates the spine morphogenesis through the activation of Rac1/WAVE/PAK/cofilin pathway, and that its ablation causes a robust and selective inhibition of excitatory synapse formation, by controlling actin dynamics. Our results revealed the underlying mechanism for the synaptic dysfunction caused by nArgBP2 downregulation that associates with analogous human BD. Moreover, since nArgBP2 interacts with key proteins involved in various neuropsychiatric disorders, our finding implies that nArgBP2 could function as a hub linking various etiological factors of different mood disorders. [BMB Reports 2016; 49(9): 457-458].
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 01030, Korea.
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 01030, Korea.
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D001523:Mental Disorders; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D013569:Synapses / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C543515:DLGAP3 protein, human; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C490755:SORBS2 protein, human; C073441:gephyrin