Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions

eLife

Kris T Delaney¹  Joan-Emma Shea¹  Yanxian Lin²  James McCarty³  Jennifer N Rauch⁴  Glenn H Fredrickson⁴  Songi Han⁵  Kenneth S Kosik⁵ 

[1] Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, United States;Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, United States;Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, United States;Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, United States;Materials Research Laboratory, University of California Santa Barbara, Santa Barbara, United States;

关键词: tau;    liquid-liquid phase separation;    phase diagram;    field-theoretic simulations;    complex coacervation;    Alzheimer's disease;   

DOI  :  10.7554/eLife.42571

来源: DOAJ

【 摘 要 】

The mechanism that leads to liquid-liquid phase separation (LLPS) of the tau protein, whose pathological aggregation is implicated in neurodegenerative disorders, is not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding whether LLPS is an equilibrium or intermediate state. We demonstrate that tau and RNA reversibly form complex coacervates. While the equilibrium phase diagram can be fit to an analytical theory, a more advanced model is investigated through field theoretic simulations (FTS) that provided direct insight into the thermodynamic driving forces of tau LLPS. Together, experiment and simulation reveal that tau-RNA LLPS is stable within a narrow equilibrium window near physiological conditions over experimentally tunable parameters including temperature, salt and tau concentrations, and is entropy-driven. Guided by our phase diagram, we show that tau can be driven toward LLPS under live cell coculturing conditions with rationally chosen experimental parameters.

【 授权许可】

Unknown