Inserm UMR837, Alzheimer and Tauopathies, 1 rue Michel Polonovski, 59045 Lille, France.
J Biol Chem. 2011 Feb 11;286(6):4566-75. doi: 10.1074/jbc.M110.199976. Epub 2010 Dec 3.
Tau, a neuronal protein involved in neurodegenerative disorders such as Alzheimer disease, which is primarily described as a microtubule-associated protein, has also been observed in the nuclei of neuronal and non-neuronal cells. However, the function of the nuclear form of Tau in neurons has not yet been elucidated. In this work, we demonstrate that acute oxidative stress and mild heat stress (HS) induce the accumulation of dephosphorylated Tau in neuronal nuclei. Using chromatin immunoprecipitation assays, we demonstrate that the capacity of endogenous Tau to interact with neuronal DNA increased following HS. Comet assays performed on both wild-type and Tau-deficient neuronal cultures showed that Tau fully protected neuronal genomic DNA against HS-induced damage. Interestingly, HS-induced DNA damage observed in Tau-deficient cells was completely rescued after the overexpression of human Tau targeted to the nucleus. These results highlight a novel role for nuclear Tau as a key player in early stress response.
tau 是一种与神经退行性疾病（如阿尔茨海默病）相关的神经元蛋白，主要被描述为微管相关蛋白，也存在于神经元和非神经元细胞的核内。然而，tau 的核形式在神经元中的功能尚未阐明。在这项工作中，我们证明急性氧化应激和轻度热应激（HS）会导致去磷酸化 tau 在神经元核内积累。通过染色质免疫沉淀实验，我们证明了内源性 tau 与神经元 DNA 相互作用的能力在 HS 后增加。彗星实验在野生型和 tau 缺失神经元培养物上进行，结果表明 tau 完全保护神经元基因组 DNA 免受 HS 诱导的损伤。有趣的是，tau 缺失细胞中观察到的 HS 诱导的 DNA 损伤在靶向细胞核的人 tau 过表达后完全得到挽救。这些结果突出了核内 tau 在早期应激反应中作为关键参与者的新作用。
