title: Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein.
abstract: Schizophrenia is a complex mental disorder with fairly high level of heritability. Dystrobrevin binding protein 1, a gene encoding dysbindin protein, is a susceptibility gene for schizophrenia that was identified by family-based association analysis. Recent studies revealed that dysbindin is involved in the exocytosis and/or formation of synaptic vesicles. However, the molecular function of dysbindin in synaptic transmission is largely unknown. To investigate the signaling pathway in which dysbindin is involved, we isolated dysbindin-interacting molecules from rat brain lysate by combining ammonium sulfate precipitation and dysbindin-affinity column chromatography, and identified dysbindin-interacting proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and liquid chromatography-tandem mass spectrometry. Proteins involved in protein localization process, including Munc18-1, were identified as dysbindin-interacting proteins. Munc18-1 was co-immunoprecipitated with dysbindin from rat brain lysate, and directly interacted with dysbindin in vitro. In primary cultured rat hippocampal neurons, a part of dysbindin was co-localized with Munc18-1 at pre-synaptic terminals. Our result suggests a role for dysbindin in synaptic vesicle exocytosis via interaction with Munc18-1.
authors: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
authors: Takao
authors: T
authors: Hikita
authors: Shinichiro
authors: S
authors: Taya
authors: Yasutaka
authors: Y
authors: Fujino
authors: Setsuko
authors: S
authors: Taneichi-Kuroda
authors: Kanae
authors: K
authors: Ohta
authors: Daisuke
authors: D
authors: Tsuboi
authors: Tomoyasu
authors: T
authors: Shinoda
authors: Keisuke
authors: K
authors: Kuroda
authors: Yusuke
authors: Y
authors: Funahashi
authors: Junko
authors: J
authors: Uraguchi-Asaki
authors: Ryota
authors: R
authors: Hashimoto
authors: Kozo
authors: K
authors: Kaibuchi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005089:Exocytosis / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D040901:Proteomics / Q000379:methods*; D051381:Rats; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D051938:Munc18 Proteins