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

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。

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.