Nuclear Tau, a Key Player in Neuronal DNA Protection

作者：Sultan Audrey; Nesslany Fabrice; Violet Marie; Begard Severine; Loyens Anne; Talahari Smail; Mansuroglu Zeyni; Marzin Daniel; Sergeant Nicolas; Humez Sandrine; Colin Morvane; Bonnefoy Eliette; Buee Luc; Galas Marie Christine^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(6): 4566-4575.

DOI：10.1074/jbc.M110.199976

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 wildtype 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.

• 出版日期2011-2
• 单位河北医科大学