Soma Mika, Wang Min, Suo Satoshi, Ishiura Shoichi
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
Neurosci Lett. 2014 Oct 17;582:120-4. doi: 10.1016/j.neulet.2014.08.046. Epub 2014 Sep 6.
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.
DTNBP1是与精神分裂症相关的关键候选基因。其蛋白质产物dysbindin-1在精神分裂症患者大脑中的表达发生改变；然而，dysbindin-1在中枢神经系统中的生理功能尚不清楚。多项研究表明，dysbindin-1和组蛋白去乙酰化酶3（HDAC3）均可被DNA依赖性蛋白激酶复合物磷酸化。在本研究中，我们调查了dysbindin-1与HDAC3之间的关系。我们发现，dysbindin-1在人神经母细胞瘤细胞和小鼠大脑中与HDAC3形成了蛋白质复合物。dysbindin-1与HDAC3之间的相互作用以亚型特异性方式发生：HDAC3与dysbindin-1A和-1B结合，但不与-1C结合。我们还发现，在存在HDAC3的情况下，dysbindin-1B在细胞核中的表达增加，相反，在存在dysbindin-1B的情况下，HDAC3的磷酸化水平增加。综上所述，这些结果确定了dysbindin-1的一种新的结合伴侣，这可能为精神分裂症神经机制的研究提供一条新途径。
