Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains
Excitatory amino acid transporter 2 associates with phosphorylated tau and is localized in neurofibrillary tangles of tauopathic brains
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DOI：
10.1016/j.febslet.2009.06.015
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发表时间：
2009-07-07
期刊：
影响因子：
3.5
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Sasaki, Kumi;Shimura, Hideki;Hattori, Nobutaka
磷酸化的tau （p-tau）是神经原纤维缠结的主要成分，是一种病理标志，可能在包括阿尔茨海默病（AD）、进行性核上性麻痹（PSP）和皮质基底变性（CBD）在内的tau病中起神经毒性作用。我们对AD、PSP和CBD尸检病例的大脑进行了各种免疫组织化学、免疫印迹和拉下分析。在这项研究中，我们发现兴奋性氨基酸转运蛋白2 （EAAT2）优先与磷酸化的tau相互作用，并定位于这类患者大脑中的神经原纤维缠结。这些结果强烈提示EAAT2在牛头病相关的神经变性中起作用，谷氨酸转运异常在牛头病的发病机制中起重要作用。结构化摘要：MINT-7148349， MINT-7148361: TAU （uniprotkb: P10636）通过下拉（MI: 0096）与EAAT2 （uniprotkb: P43004）物理相互作用（MI: 0914） MINT-7148372, MINT-7148384: TAU （uniprotkb: P10636）通过抗诱饵共免疫沉淀（MI: 0006）与EAAT2 （uniprotkb: P43004）物理相互作用（MI: 0914） (C) 2009欧洲生化学会联合会。Elsevier b.v.版权所有。
Phosphorylated tau (p-tau) is the principal component of neurofibrillary tangles, a pathological hallmark, and likely plays a neurotoxic role in tauopathies including Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We subjected brains from autopsy cases of AD, PSP, and CBD to a variety of immunohistochemical, immunoblotting, and pull-down assays. In this study, we show that excitatory amino acid transporter 2 (EAAT2) preferentially interacted with phosphorylated tau and was localized in neurofibrillary tangles in the brains of such patients. These results strongly indicate that EAAT2 acts in tauopathy-related neurodegeneration, and abnormalities in glutamate transport play an important role in the pathogenesis of tauopathies.Structured summary:MINT-7148349, MINT-7148361: TAU (uniprotkb: P10636) physically interacts (MI: 0914) with EAAT2 (uniprotkb: P43004) by pull-down (MI: 0096)MINT-7148372, MINT-7148384: TAU (uniprotkb: P10636) physically interacts (MI: 0914) with EAAT2 (uniprotkb: P43004) by anti bait coimmunoprecipitation (MI: 0006) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.