Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein.
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.
Hikita
Takao
T
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8550, Japan.
Taya
Shinichiro
S
Fujino
Yasutaka
Y
Taneichi-Kuroda
Setsuko
S
Ohta
Kanae
K
Tsuboi
Daisuke
D
Shinoda
Tomoyasu
T
Kuroda
Keisuke
K
Funahashi
Yusuke
Y
Uraguchi-Asaki
Junko
J
Hashimoto
Ryota
R
Kaibuchi
Kozo
K
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*
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D051938:Munc18 Proteins