RT Journal Article
SR Electronic
T1 Liquid-liquid phase separation and fibrillization of tau are independent processes with overlapping conditions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 702126
DO 10.1101/702126
A1 Yanxian Lin
A1 Yann Fichou
A1 Zhikai Zeng
A1 Nicole Y. Hu
A1 Songi Han
YR 2019
UL http://biorxiv.org/content/early/2019/07/13/702126.abstract
AB Amyloid aggregation of the microtubule binding protein tau is a hallmark of Alzheimer’s disease and many other neurodegenerative diseases. Recently, tau has been found to undergo liquid-liquid phase separation (LLPS) near physiological conditions. Although LLPS and aggregation have been shown to simultaneously occur under certain common conditions, it remains to be seen whether tau LLPS promotes aggregation, or if they are two independent processes. In this study, we address this question by combining multiple biochemical and biophysical assays in vitro. We investigated the impacts of LLPS on tau aggregation at three stages: conformation of tau, kinetics of aggregation and fibril quantity. We showed that none of these properties are influenced directly by LLPS, while amyloid aggregation propensity of tau can be altered without affecting its LLPS behavior. LLPS and amyloid aggregation of tau occur under overlapping conditions of enhanced intermolecular interactions and localization, but are two independent processes.