Analysis of the pathogenic mechanism for neuropsychiatric disease-like abnormal behavior in IRBIT knockout mouse

IRBIT基因敲除小鼠神经精神疾病样异常行为发病机制分析

• 批准号: 24700389
• 负责人: KAWAAI Katsuhiro
• 金额: $ 2.83万
• 依托单位: Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24700389/
• 关键词: IRBIT; 多動障害; モノアミン; CaMKII; NBC1; pH; DIA; 行動異常; TH; リン酸化

An IP3R binding protein termed IRBIT (IP3R binding protein released with inositol 1,4,5-trisphosphate) that interacts with the IP3 binding core domain of IP3R and regulate the IP3 sensitivity of IP3R. Recently, we identified calcium/calmodulin-dependent kinase II alpha (CaMKIIalpha) as an IRBIT binding protein. In this study, we investigated the effect of IRBIT deletion on the monoamine (dopamine and norepinephrine) synthesis and intracellular pH regulation to explain the function of IRBIT in the central nervous system. We found that IRBIT regulated the phosphoryaltion state of TH by CaMKIIalpha. In addition, IRBIT contributed the regulation of intracellular pH by NBC1 in the neuron and astrocyte.

一种IP3R结合蛋白，称为IRBIT(与1，4，5-三磷酸肌醇释放的IP3R结合蛋白)，它与IP3R的IP3结合核心区相互作用，调节IP3R的IP3敏感性。最近，我们发现钙/钙调蛋白依赖的蛋白IIα(CaMKIIpha)是一种IRbit结合蛋白。在这项研究中，我们研究了Irbit缺失对单胺(多巴胺和去甲肾上腺素)合成和细胞内pH调节的影响，以解释Irbit在中枢神经系统中的功能。我们发现Irbit通过CaMKIIpha调节TH的磷酸化状态。此外，在神经元和星形胶质细胞中，Irbit还参与了NBC1对细胞内pH的调节。