Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions.
Alzheimer's disease
complex coacervation
computational biology
field-theoretic simulations
liquid-liquid phase separation
neuroscience
none
phase diagram
protein droplet
systems biology
tau
tauopathies
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
05 04 2019
05 04 2019
Historique:
received:
04
10
2018
accepted:
06
03
2019
entrez:
6
4
2019
pubmed:
6
4
2019
medline:
29
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30950394
doi: 10.7554/eLife.42571
pii: 42571
pmc: PMC6450672
doi:
pii:
Substances chimiques
Colloids
0
tau Proteins
0
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Rainwater Foundation
ID : Tau Consortium
Pays : International
Organisme : NIA NIH HHS
ID : RO1AG05605
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056058
Pays : United States
Organisme : Santa Barbara Foundation
ID : Tri-Counties Blood Bank Fellowship
Pays : International
Organisme : National Science Foundation
ID : MCB-1716956
Pays : International
Organisme : National Science Foundation
ID : MRSEC Program, Award No. DMR 1720256
Pays : International
Informations de copyright
© 2019, Lin et al.
Déclaration de conflit d'intérêts
YL, JM, JR, KD, KK, GF, JS, SH No competing interests declared
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