Amyloid aggregation of tau protein is implicated in neurodegenerative diseases, yet its facilitating factors are poorly understood. Recently, tau has been shown to undergo liquid liquid phase separation (LLPS) both in vivo and in vitro. LLPS was shown to facilitate tau amyloid aggregation in certain cases, while independent of aggregation in other cases. It is therefore important to understand the differentiating properties that resolve this apparent conflict. We report on a model system of hydrophobically driven LLPS induced by high salt concentration (LLPS-HS), and compare it to electrostatically driven LLPS represented by tau-RNA/heparin complex coacervation (LLPS-ED). We show that LLPS-HS promotes tau protein dehydration, undergoes maturation and directly leads to canonical tau fibrils, while LLPS-ED is reversible, remains hydrated and does not promote amyloid aggregation. We show that the nature of the interaction driving tau condensation is the differentiating factor between aggregation-prone and aggregation-independent LLPS.

中文翻译：

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疏水相互作用驱动的tau液-液相分离促进tau的原纤维化

tau蛋白的淀粉样蛋白聚集与神经退行性疾病有关，但其促进因素知之甚少。近来，已经证明tau在体内和体外均经历了液相分离（LLPS）。LLPS在某些情况下可促进tau淀粉样蛋白的聚集，而在其他情况下则独立于聚集。因此，重要的是要了解解决这种明显冲突的区别属性。我们报告了由高盐浓度（LLPS-HS）诱导的疏水驱动LLPS的模型系统，并将其与以tau-RNA /肝素复合物凝聚（LLPS-ED）代表的静电驱动LLPS进行了比较。我们显示LLPS-HS促进tau蛋白脱水，经历成熟并直接导致经典tau纤维，而LLPS-ED是可逆的，保持水分，不促进淀粉样蛋白聚集。我们表明，驱动tau缩合反应的相互作用的本质是易于聚集和独立于聚集的LLPS之间的区别因素。