Tau Condensates

Kenneth S. Kosik*, Songi Han

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

11 Scopus citations

Abstract

Many proteins, particularly those that are intrinsically disordered and carry charges have a tendency to undergo liquid liquid phase separation (LLPS). Phase separation is a widespread mechanism by which cells concentrate a set of proteins to perform molecular reactions, and appear to compartmentalize molecular functions. Among the intrinsically disordered proteins are a subset that tend to form solid inclusions in cells and contribute to the pathology of several neurodegenerative diseases. Among this subset is the tau protein, a critically important inclusion in a class of conditions known as the tauopathies, which include Alzheimer’s disease. Tau in neurons strongly and selectively associates with RNA species, most notably tRNA with a nanomolar dissociation constant. Furthermore, tau and RNA, under charge matching conditions, undergo LLPS in a process known as complex coacervation. Tau-RNA LLPS is reversible, and can persist for more than 15 h without subsequent fibrilization, although after longer time periods β-sheet content can be detected by thioflavin T. These findings suggest that LLPS tau droplets or condensates can be placed on a pathway to fibrillization and be arrested by solidification or dissolve into a soluble state, depending on the condition at hand, suggesting a regulatory and physiological role for the phase separated state of tau.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages327-339
Number of pages13
DOIs
StatePublished - 2019

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1184
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Coacervation
  • Electron paramagnetic resonance
  • Frontotemporal dementia
  • Liquid-liquid phase separation
  • Membraneless organelles
  • RNA
  • Tau droplets

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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