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Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia‐related protein
Author(s) -
Hikita Takao,
Taya Shinichiro,
Fujino Yasutaka,
TaneichiKuroda Setsuko,
Ohta Kanae,
Tsuboi Daisuke,
Shinoda Tomoyasu,
Kuroda Keisuke,
Funahashi Yusuke,
UraguchiAsaki Junko,
Hashimoto Ryota,
Kaibuchi Kozo
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06257.x
Subject(s) - synaptic vesicle , synaptotagmin 1 , biology , chemistry , exocytosis , neurotransmission , snap25 , microbiology and biotechnology , biochemistry , vesicle , secretion , receptor , membrane
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.