Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein

• Published in: Journal of neurochemistry 2009-09, Vol.110 (5), p.1567-1574
• Main Authors: Hikita, Takao, Taya, Shinichiro, Fujino, Yasutaka, Taneichi-Kuroda, Setsuko, Ohta, Kanae, Tsuboi, Daisuke, Shinoda, Tomoyasu, Kuroda, Keisuke, Funahashi, Yusuke, Uraguchi-Asaki, Junko, Hashimoto, Ryota, Kaibuchi, Kozo
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Aminoacid receptors (glycine, glutamate, gaba); Animals; Binding sites; Biochemistry; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell receptors; Cell structures and functions; Dysbindin; Dystrophin-Associated Proteins; Exocytosis - genetics; Fundamental and applied biological sciences. Psychology; Hippocampus - metabolism; Humans; Medical sciences; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Munc18 Proteins - genetics; Munc18 Proteins - metabolism; Munc18-1; Neurology; Protein Binding - genetics; Proteins; proteomics; Proteomics - methods; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Schizophrenia; Schizophrenia - genetics; Schizophrenia - metabolism; susceptibility gene
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06257.x

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.