Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3

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Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3

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Mika Soma, Min Wang, Satoshi Suo, Shoichi Ishiura ∗ Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan

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h i g h l i g h t s • • • •

Dysbindin-1 interacts with HDAC3 in vivo. Dysbindin-1A and -1B interact with HDAC3 but -1C does not. Dysbindin-1B expression is increased in the nucleus in the presence of HDAC3. The phosphorylation level of HDAC3 increased in the presence of dysbindin-1B.

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Article history: Received 2 May 2014 Received in revised form 13 August 2014 Accepted 26 August 2014 Available online xxx

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Keywords: Schizophrenia Dysbindin-1 HDAC3 Interaction Isoform Phosphorylation

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1. Introduction

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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. © 2014 Published by Elsevier Ireland Ltd.

Schizophrenia is a chronic mental disorder characterized by positive symptoms such as hallucinations and delusions, and negative symptoms such as dullness of thinking and behavior, as well as cognitive disorders in memory and learning. Numerous studies have suggested that genetic factors contribute to schizophrenia, and several genes, including DISC1, NRG1, and DTNBP1, have been identified as schizophrenia susceptibility genes [14,19,20]. DTNBP1 is situated at chromosomal locus 6p22.3, a location with established linkage to schizophrenia [17,21,28]. DTNBP1 has several SNPs that are suggested to influence the risk of developing schizophrenia [18,20]. Since the SNPs in DTNBP1 are in an intron, and not in an exon, they do not affect the amino acid sequence of the encoded protein, dysbindin-1; rather, they regulate the expression of dysbindin1 mRNA and protein [2]. Recent postmortem brain studies have

∗ Corresponding author. Tel.: +81 3 5454 6739; fax: +81 3 5454 6739. E-mail address: [email protected] (S. Ishiura).

shown that the expression of dysbindin-1 mRNA and protein is reduced in the brains of schizophrenic patients [24,25,29,30]. Furthermore, it has been reported that dysbindin-1-deficient mice are less active and display reduced novelty-seeking behavior, similar to the negative symptoms of schizophrenia, and that they show cognitive deficiencies in learning and memory [1,3,5,7,9,23]. Therefore, it is thought that dysbindin-1 expression is reduced in schizophrenic patients, preventing the protein from fulfilling its normal physiological function and contributing to the symptoms of schizophrenia. Although most studies have addressed the function of dysbindin-1 in the cytoplasm, dysbindin-1 is also found in the nucleus [16]. It has been reported that dysbindin-1 interacts with nuclear proteins such as nuclear transcription factor Y beta (NF-YB) and the DNA-dependent protein kinase (DNA-PK) complex [15,16]. Dysbindin-1 interacts with and is phosphorylated by the DNAPK complex [16]. The DNA-PK complex also interacts with and phosphorylates histone deacetylase 3 (HDAC3), which is a transcriptional regulator [11]. HDAC3 is particular in Class I HDACs, because HDAC3 is able to shuttle between the cytoplasm and

http://dx.doi.org/10.1016/j.neulet.2014.08.046 0304-3940/© 2014 Published by Elsevier Ireland Ltd.

Please cite this article in press as: M. Soma, et al., Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3, Neurosci. Lett. (2014), http://dx.doi.org/10.1016/j.neulet.2014.08.046

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the nucleus in certain conditions [22,31]. The knockout of HDAC3 in mouse hippocampus enhances long-term memory, suggesting that HDAC3 is a negative regulator of long-term memory formation [12]. In addition, HDAC inhibitors are expected to be effective drugs for the treatment of psychiatric disorders, including schizophrenia, based on evidence showing that histone acetylation is reduced in patients with psychiatric disorders [4,8,27]. Because both dysbindin-1 and HDAC3 are phosphorylated by the DNA-PK complex, we sought to investigate the relationship between these two proteins. The proposed overlap in function and subcellular distribution profiles between dysbindin-1 and HDAC3 strongly suggest a specific interaction; however, this hypothesis has not yet been directly tested. In this study, we show that dysbindin-1 isoforms A and B, but not C, interact with HDAC3. In addition, the expression of dysbindin-1B increases in the nucleus in the presence of HDAC3, and it facilitates the phosphorylation of HDAC3.

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2. Materials and methods

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2.1. Antibodies

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Rabbit polyclonal antibodies against dysbindin-1 were generated according to the previous report [16]. Anti-V5 and -lamin B mouse monoclonal antibodies were purchased from Life Technologies (Carlsbad, CA). The following rabbit polyclonal antibodies were purchased from the indicated vendors: anti-HDAC3 (Abcam, Cambridge, UK), anti-phospho-HDAC3, antimyc, and anti-␣-tubulin (all Cell Signaling Technology, Inc., Beverly, MA). Anti-GST goat polyclonal antibodies were purchased from GE Healthcare (Cleveland, OH). 2.2. Plasmid construction The cDNAs encoding HDAC3 and the three isoforms of human dysbindin-1 were cloned from a human fetal brain cDNA library (BD Biosciences, San Jose, CA) by polymerase chain reaction. The cDNAs were subcloned into pcDNA3.1 (Invitrogen, Carlsbad, CA) or pGEX-5X-1 (GE Healthcare), which contain a hexahistidine tag at the C-terminus. Myc-dysbindin-1 contained six myc tags at the N-terminus of dysbindin-1. GST-dysbindin-1 contained a GST tag at the N-terminus and three His tags the C-terminus of dysbindin1. V5-HDAC3 contained a V5 tag at the C-terminus of HDAC3. All constructs were confirmed by sequencing [16]. 2.3. Expression and purification of GST and GST-dysbindin-1 and GST pull-down assay

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GST and GST-dysbindin-1 were purified and GST pull-down assay was performed according to the previous report [16].

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2.4. Co-immunoprecipitation

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Lysates (800 ␮g per sample) diluted in 500 ␮L of NP-40 buffer were precleared with 30 ␮L of Protein G Sepharose 4 Fast Flow beads (GE Healthcare) for 2 h at 4 ◦ C. The precleared lysates and antibodies linked to Protein G Sepharose 4 Fast Flow beads were incubated for 4 h at 4 ◦ C. After washing, sample buffer was added, and the samples were boiled for 5 min at 100 ◦ C. The precipitates were analyzed by SDS-PAGE and immunoblotting.

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2.5. Subcellular fractionation

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Subcellular fractionation was performed with a Qproteome Cell Compartment Kit (Qiagen) according to the manufacturer’s protocol.

Fig. 1. Interaction between endogenous dysbindin-1 and HDAC3. (A) Coimmunoprecipitation of dysbindin-1 using anti-HDAC3 antibodies in SH-SY5Y cells. (B) Co-immunoprecipitation of HDAC3 using anti-dysbindin-1 antibodies in SHSY5Y cells. (C) Co-immunoprecipitation of HDAC3 using anti-dysbindin-1 antibodies in mouse forebrain. IP, immunoprecipitation.

2.6. HDAC3 phosphorylation level analysis Immunoprecipitation was performed using 500 ␮L of a lysate prepared from HEK293 cells expressing myc-dysbindin-1 and V5HDAC3, and anti-V5 antibody-linked Protein G Sepharose 4 Fast Flow beads. After washing, the precipitates were divided into two aliquots. To both aliquots, 30 ␮L of CIAP buffer (50 mM Tris–HCl [pH 9.0], 100 mM NaCl, and 1 mM MgCl2 ) were added. To one aliquot, 1 ␮L of calf intestinal alkaline phosphatase (Takara Bio Inc., Otsu, Japan) was also added. The precipitates ware incubated overnight at 37 ◦ C. The precipitates were analyzed by SDS-PAGE and immunoblotting. 2.7. Immunoblotting Samples were separated by SDS-PAGE and transferred to nitrocellulose membranes (Protran; Whatman, GE Healthcare). The membranes were blocked with 5% skim milk in TBST (100 mM Tris–HCl [pH 7.5], 150 mM NaCl, and 0.05% Tween 20) for 1 h at room temperature and then incubated overnight at 4 ◦ C with primary antibodies in 5% skim milk. After washing, the membranes were incubated for 1 h with horseradish peroxidase-conjugated secondary antibodies at room temperature. The secondary antibodies were purchased from the indicated vendors: anti-rabbit and -mouse IgG (Cell Signaling Technology, Inc.) and anti-goat IgG (Santa Cruz Biotechnology). Immunoreactive bands were visualized by enhanced chemiluminescence (GE Healthcare) and scanned using an LAS 3000 scanner (Fujifilm Co. Ltd., Tokyo, Japan).

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3. Results

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3.1. Endogenous dysbindin-1 interacts with endogenous HDAC3

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To provide evidence for the existence of a dysbindin-1-HDAC3 complex, we first examined whether dysbindin-1 could be coimmunoprecipitated with HDAC3. As shown in Fig. 1A and B, extracts of human neuroblastoma SH-SY5Y cells were subjected to immunoprecipitation with anti-HDAC3 or anti-dysbindin-1 antibodies and an IgG control, followed by immunoblotting for endogenous dysbindin-1 or HDAC3, respectively. Co-immunoprecipitation also demonstrated an interaction between dysbindin-1 and HDAC3 in solubilized mouse forebrain (Fig. 1C). These results suggest that dysbindin-1 interacts with HDAC3 in vivo.

Please cite this article in press as: M. Soma, et al., Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3, Neurosci. Lett. (2014), http://dx.doi.org/10.1016/j.neulet.2014.08.046

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Fig. 2. Identification of the dysbindin-1 isoforms involved in the interaction with HDAC3. (A) Schematic representation of dysbindin-1 isoforms. (B) Western blotting for V5-HDAC3 after affinity precipitation with GST-dysbindin-1 or GST alone, using lysates of HEK293 cells transfected with V5-HDAC3 (upper panel). GST was used as a control (lower panel). (C) Co-immunoprecipitation of myc-dysbindin-1 using anti-V5 antibodies with lysates of HEK293 cells co-transfected with myc-dysbindin1 and V5-HDAC3. The lysates (left panel) and immunoprecipitates (right panel) are shown. Myc-dysbindin-1 (upper panel) and V5-HDAC3 (lower panel) were detected.

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3.2. Dysbindin-1 interacts with HDAC3 in an isoform-specific manner Among the proteins of the dysbindin family, dysbindin-1 is the only one that is reportedly associated with schizophrenia. DTNBP1, the gene encoding dysbindin-1, has three major transcript isoforms (Fig. 2A) in humans of approximately 50, 37, and 33 kDa, denoted dysbindin-1A, -1B, and -1C, respectively [26]. Expression of these isoforms differs in terms of region, subcellular localization, and developmental time-course [10,25]. To identify the isoform(s) of dysbindin-1 that interact with HDAC3, we constructed GST fusion proteins encoding the A to C isoforms of human dysbindin-1. Affinity pull-down assays of proteins from lysates of HEK293 cells transfected with V5-HDAC3 were performed, with GST alone as a control. As shown in Fig. 2B, dysbindin-1A and -1B, but not -1C or GST alone, precipitated V5-HDAC3, indicating that dysbindin-1 interacts with HDAC3 in an isoform-specific manner. To further confirm this isoform-specific interaction, we also performed co-immunoprecipitation using HEK293 cells co-transfected with myc-tagged dysbindin-1 (isoforms A–C) and V5-HDAC3. As illustrated in Fig. 2C, myc-tagged dysbindin-1A and -1B, but not 1C, co-immunoprecipitated with V5-HDAC3, in agreement with our

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Fig. 3. Subcellular distribution and change in the localization of dysbindin-1 and HDAC3. (A) Subcellular distribution of dysbindin-1 and HDAC3. ␣-Tubulin and lamin B1 were used as cytoplasmic and nuclear markers, respectively. Cy: cytoplasmic fraction; Nu: nuclear fraction. (B) Change in dysbindin-1 and HDAC3 localization in the presence or absence of each other. (C–E) Quantitation of the nuclear expression of dysbindin-1A (C), -1B (D) and -1C (E). The signal intensity of dysbindin-1 was standardized to the corresponding protein band of lamin B1. The value of the control was designated as 1. *Significantly different from the control group (*P < 0.05, n = 5); Student’s t-test.

affinity pull-down results. Taken together, these data indicate that dysbindin-1 interacts with HDAC3 in an isoform-specific manner. 3.3. Formation of the dysbindin-1-HDAC3 complex influences the subcellular distribution of dysbindin-1B Previous studies demonstrated that endogenous dysbindin-1 localizes mainly to the cytoplasm, with some diffuse expression in the nucleus [6,16,], while HDAC3, is able to shuttle between the cytoplasm and the nucleus in certain conditions [22,31]. This overlapping subcellular distribution suggests that the dysbindin1-HDAC3 complex regulates the localization of dysbindin-1 and/or HDAC3. To confirm the subcellular distribution of dysbindin-1 and HDAC3 in our system, we performed subcellular fractionation of HEK293 cells transfected with myc-dysbindin-1 (isoforms A–C) or V5-HDAC3, followed by immunoblotting. Lamin B1 and ␣tubulin were used as nuclear and cytosolic markers, respectively. Dysbindin-1 (isoforms A–C) was localized primarily in the cytoplasmic fraction, with a small amount in the nuclear fraction (Fig. 3A). Next to study the effect of the dysbindin-1-HDAC3 complex, we co-transfected HEK293 cells with myc-dysbindin-1 (isoforms A–C) and V5-HDAC3. As shown in Fig. 3B, both dysbindin-1A and -1B exhibited increased nuclear localization in the presence of HDAC3; however, only the increase in dysbindin-1B was statistically significant (Fig. 3D). A localization change for HDAC3 was not observed in either the nuclear or cytoplasmic fraction (Fig. 3B). Taken together,

Please cite this article in press as: M. Soma, et al., Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3, Neurosci. Lett. (2014), http://dx.doi.org/10.1016/j.neulet.2014.08.046

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Fig. 4. The HDAC3 phosphorylation level is altered in the presence of dysbindin1. (A) Western blotting for phospho-HDAC3 and V5-HDAC3 in the presence of dysbindin-1. (B) Quantitation of phospho-HDAC3 in the presence of dysbindin-1. The signal intensity of phospho-HDAC3 was standardized to the corresponding protein band of V5-HDAC3. The value of the control was designated as 1.*Significantly different from the control group (*P < 0.05, n = 6); Dunnett’s test.

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these results suggest that dysbindin-1B translocates to the nucleus in the presence of HDAC3.

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3.4. Dysbindin-1B promotes HDAC3 phosphorylation

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We next investigated the functional significance of dysbindin1-HDAC3 complex formation. Because dysbindin-1 and HDAC3 are reported to be phosphorylated by the same DNA-PK complex [11,16], we assessed the influence of the dysbindin-1-HDAC3 complex on HDAC3 phosphorylation in HEK293 cells co-transfected with myc-dysbindin-1 (isoforms A–C) and V5-HDAC3. HDAC3 was immunoprecipitated using anti-V5 antibodies, and HDAC3 phosphorylation was detected using anti-phospho-HDAC3 (Ser424) antibodies. As a negative control, immunoprecipitation was carried out side-by-side in the presence of alkaline phosphatase to confirm the specificity of the phosphorylation antibody. As shown in Fig. 4A, the phosphorylation of HDAC3 at Ser424 was significantly increased by almost two-fold when dysbindin-1B, but not -1A or -1C, was co-transfected. The phospho-HDAC3 band intensities were quantified and normalized to the expression level of HDAC3, as shown in Fig. 4B. These data suggest that the interaction between dysbindin-1B and HDAC3 regulates HDAC3 phosphorylation.

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4. Discussion

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spliced isoforms of dysbindin-1. As shown in Fig. 2A, dysbindin-1A is the full-length form while -1B has a different, shorter C-terminus from -1A, and -1C lacks the N-terminus of -1A. Based on our results, the domain of dysbindin-1 required for the interaction with HDAC3 is likely to be in the N-terminus and common to -1A and -1B. Future studies are required to delineate the specific region(s) involved in this interaction. Previous reports have shown that dysbindin-1 is expressed in the nuclei of hippocampal neurons in vivo [24], and that dysbindin-1 has a functional nuclear export signal facilitating nucleocytoplasmic shuttling of dysbindin-1, which affects its regulation of synapsin I expression [6]. However, the precise function of dysbindin-1 in the nucleus remains largely unknown. Therefore, we examined whether the dysbindin-1-HDAC3 complex affects the subcellular localization of dysbindin-1 (A–C) or HDAC3. Surprisingly, although both dysbindin-1A and -1B bound HDAC3, only dysbindin-1B exhibited a significant increase in nuclear localization in the presence of HDAC3, as demonstrated by subcellular fractionation. Although Oyama et al. [16] reported that dysbindin-1 bound DNA-PK in an isoform-dependent manner, functional differences among these three isoforms remain unclear. Future studies are required to investigate whether this is due to the difference in amino acid sequence between dysbindin-1A and -1B or other factors (e.g., subcellular distribution). Previous reports have also shown that dysbindin-1 can be exported from the nucleus to the cytoplasm by exportin-1/CRM1-mediated nuclear export. Furthermore, nuclear dysbindin-1 transcriptionally regulates synapsin I gene expression [6]. Therefore, it is possible that in our system the dysbindin-1B-HDAC3 complex interfered with the interaction between dysbindin-1 and CRM1, inhibiting the nucleocytoplasmic shuttling of dysbindin-1, in addition to its regulation of synapsin I expression. Further study is required to gain a better understanding of the detailed molecular mechanisms through which the dysbindin-1-HDAC3 complex translocates from the cytoplasm to the nucleus. Interestingly, we also found that, of the three dysbindin-1 isoforms, HDAC3 phosphorylation increased only in the presence of dysbindin-1B. Since dysbindin-1A and -1B have different C-termini, we hypothesize that C-terminal sequence divergence may be the basis of their isoform-specific interaction properties. Previous studies suggested that HDAC3 phosphorylation enhances the deacetylase activity of HDAC3 [11,32]. In this study, we demonstrated that the dysbindin-1-HDAC3 complex facilitated HDAC3 phosphorylation, possibly leading to regulation of its deacetylase activity. HDAC3 forms a complex with NCoR and SMRT, and this complex deacetylates histones such as H3 and H4 [13]. HDAC3 complexes also interact with transcription factors and repress transcription [13]. Dysbindin-1 may affect transcription through an interaction with HDAC3. In conclusion, in this study we provide the first evidence of an interaction between dysbindin-1 and HDAC3 that regulates the subcellular distribution of dysbindin-1 and HDAC3 phosphorylation. Further study is needed to elucidate the influence of dysbindin-1 on the downstream pathway of HDAC3, such as the histone acetylation, possibly providing a novel target for the treatment of schizophrenia.

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In this study, we demonstrated an interaction between dysbindin-1 and HDAC3 in vivo, in both human neuroblastoma cells and mouse brain tissue. In addition, we showed by GST pull-down and co-immunoprecipitation assays that dysbindin-1A and -1B, but not -1C, interact with HDAC3. This isoform-specific interaction may be attributable to the differences in amino acid sequence of the

This work was supported by an Intramural Research Grants (23- Q2 5) for Neurological and Psychiatric Disorders of NCNP from the Ministry of Health, Labor and Welfare, Japan, and Comprehensive Q3 Research on Disability Health and Welfare, the Ministry of Health, Labor and Welfare, Japan (to S.I.).

Please cite this article in press as: M. Soma, et al., Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3, Neurosci. Lett. (2014), http://dx.doi.org/10.1016/j.neulet.2014.08.046

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Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/ j.neulet.2014.08.046. References [1] S.K. Bhardwaj, M. Baharnoori, B. Sharif-Askari, A. Kamath, S. Williams, L.K. Srivastava, Behavioral characterization of dysbindin-1-deficient sandy mice, Behav. Brain Res. 197 (2009) 435–441. [2] N.J. Brav, P.R. Buckland, M.J. Owen, M.C. O’Donovan, Cis-acting variation in the expression of a high proportion of genes in human brain, Hum. Genet. 113 (2003) 143–153. [3] G.C. Carlson, K. Talbot, T.B. Halene, M.J. Gandal, H.A. Kazi, L. Schlosser, Q.H. Phung, R.E. Gur, S.E. Arnold, S.J. Siegel, Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia, Proc. Natl. Acad. Sci. U. S. A. 108 (43) (2011) E962–E970. [4] D.S. Cha, P.A. Kudlow, A. Baskaran, R.B. Mansur, R.S. McIntyre, Implications of epigenetic modulation for novel treatment approaches in patients with schizophrenia, Neuropharmacology 77 (2014) 481–486. [5] M.M. Cox, A.M. Tucker, J. Tang, K. Talbot, D.C. Richer, L. Yeh, S.E. Arnold, Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6 J genetic background, Genes Brain Behav. 8 (2009) 390–397. [6] E. Fei, X. Ma, C. Zhu, T. Xue, J. Yan, Y. Xu, J. Zhou, G. Wang, Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related protein, regulates synapsin I expression, J. Biol. Chem. 285 (2010) 38630–38640. [7] Y.Q. Feng, Z.Y. Zhou, X. He, H. Wang, X.L. Guo, C.J. Hao, Y. Guo, X.C. Zhen, W. Li, Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia, Schizophr. Res. 106 (2008) 218–228. [8] D.P. Gavin, S. Kartan, K. Chase, D.R. Grayson, R.P. Sharma, Reduced baseline acetylated histone 3 levels, and a blunted response to HDAC inhibition in lymphocyte cultures from schizophrenia subjects, Schizophr. Res. 103 (2008) 330–332. [9] S. Hattori, T. Murotani, S. Matsuzaki, T. Ishizuka, N. Kumamoto, M. Takeda, M. Tohyama, A. Yamatodani, H. Kunugi, R. Hashimoto, Behavioral abnormalities and dopamine reductions in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia, Biochem. Biophys. Res. Commun. 373 (2008) 298–302. [10] H. Ito, R. Morishita, T. Shinoda, I. Iwamoto, K. Sudo, K. Okamoto, K. Nagata, Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation, Mol. Psychiatry 15 (2010) 976–986. [11] M. Jeyakumar, X.F. Liu, H. Erdjument-Bromage, P. Tempst, M.K. Bagchi, Phosphorylation of thyroid hormone receptor-associated nuclear receptor corepressor holocomplex by the DNA-dependent protein kinase enhances its histone deacetylase activity, J. Biol. Chem. 282 (2007) 9312–9322. [12] S.C. McQuown, R.M. Barrett, D.P. Matheos, R.J. Post, G.A. Rogge, T. Alenghat, S.E. Mullican, S. Jones, J.R. Rusche, M.A. Lazar, M.A. Wood, HDAC3 is a critical negative regulator of long-term memory formation, J. Neurosci. 31 (2011) 764–774. [13] S.C. McQuown, M.A. Wood, HDAC3 and the molecular brake pad hypothesis, Neurobiol. Learn. Mem. 96 (2011) 27–34. [14] J.K. Millar, J.C. Wilson-Annan, S. Anderson, S. Christie, M.S. Taylor, C.A. Semple, R.S. Devon, D.M. St Clair, W.J. Muir, D.H. Blackwood, D.J. Porteous, Disruption of two novel genes by a translocation co-segregating with schizophrenia, Hum. Mol. Genet. 9 (2000) 1415–1423. [15] H. Okuda, R. Kuwahara, S. Matsuzaki, S. Miyata, N. Kumamoto, T. Hattori, S. Shimizu, K. Yamada, K. Kawamoto, R. Hashimoto, M. Takeda, T. Katayama, M. Tohyama, Dysbindin regulates the transcriptional level of myristoylated alanine-rich protein kinase C substrate via the interaction with NF-YB in mice brain, PLoS ONE 5 (2010) e8773. [16] S. Oyama, H. Yamakawa, N. Sasagawa, Y. Hosoi, E. Futai, S. Ishiura, Dysbindin-1, a schizophrenia-related protein, functionally interacts with the

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Please cite this article in press as: M. Soma, et al., Dysbindin-1, a schizophrenia-related protein, interacts with HDAC3, Neurosci. Lett. (2014), http://dx.doi.org/10.1016/j.neulet.2014.08.046

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