Korea Institute of Science and Technology (KIST), Brain Science Institute, Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Seoul 02792, Korea.
Department of Life Science, Korea University, Seoul 02841, Korea.
Int J Mol Sci. 2018 Sep 29;19(10):2978. doi: 10.3390/ijms19102978.
Tau is a neuron-specific microtubule-binding protein that stabilizes microtubules. It is generally thought that highly phosphorylated tau dissociates from microtubules and becomes insoluble aggregates, leading to neuronal degeneration. Due to the implication of tau aggregation in neurodegenerative disorders, including Alzheimer's disease, great efforts have been made to identify the tau aggregation process. However, tau interaction with tubulin during the aggregation process remains largely unknown. To scrutinize the tau-tubulin interaction, we generated a cell model that enables visualization of the tau-tubulin interaction in a living cell using the Bifluorescence Complementation (BiFC) Technique. Upon diverse chemical stimulation that induced tau pathology, tau-tubulin BiFC cells showed significantly increased levels of BiFC fluorescence, indicating that tau aggregates together with tubulin. Our results suggest that tubulin should be considered as a key component in the tau aggregation process.
tau 是一种神经元特异性微管结合蛋白，可稳定微管。一般认为，高度磷酸化的 tau 从微管上脱离并形成不溶性聚集物，导致神经元变性。由于 tau 聚集与神经退行性疾病（包括阿尔茨海默病）有关，因此人们做出了巨大努力来识别 tau 聚集过程。然而，tau 在聚集过程中与微管的相互作用在很大程度上仍不清楚。为了仔细研究 tau-微管相互作用，我们构建了一个细胞模型，该模型使用双荧光互补（BiFC）技术可在活细胞中可视化 tau-微管相互作用。在诱导 tau 病变的各种化学刺激下，tau-微管 BiFC 细胞显示出 BiFC 荧光显著增加，表明 tau 与微管聚集在一起。我们的结果表明，微管应该被视为 tau 聚集过程中的关键组成部分。
