title: Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3.
abstract: DTNBP1 is a key candidate gene associated with schizophrenia. The expression of its protein product, dysbindin-1, is altered in the brains of schizophrenic patients; however, the physiological functions of dysbindin-1 in the central nervous system are unclear. Several studies have shown that both dysbindin-1 and histone deacetylase 3 (HDAC3) can be phosphorylated by the DNA-dependent protein kinase complex. In this study, we investigated the relationship between dysbindin-1 and HDAC3. We found that dysbindin-1 formed a protein complex with HDAC3 in human neuroblastoma cells and in mouse brain. The interaction between dysbindin-1 and HDAC3 occurred in an isoform-specific manner: HDAC3 coupled with dysbindin-1A and -1B, but not -1C. We also found that dysbindin-1B expression was increased in the nucleus in the presence of HDAC3, and, conversely, that the phosphorylation level of HDAC3 increased in the presence of dysbindin-1B. Taken together, these results identify a novel binding partner for dysbindin-1, which may potentially provide a new avenue for research into the neurological mechanisms of schizophrenia.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Soma
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suo
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan. Electronic address: cishiura@mail.ecc.u-tokyo.ac.jp.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D016548:Prosencephalon / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D006655:Histone Deacetylases; D020033:Protein Isoforms; D000099186:Histone Deacetylase 3; C432416:DTNBP1 protein, human
keywords: Dysbindin-1; HDAC3; Interaction; Isoform; Phosphorylation; Schizophrenia