Disease-Associated Tau Phosphorylation Hinders Tubulin Assembly within Tau Condensates.
IDP
NMR spectroscopy
liquid-liquid phase separation
phosphorylation
tau
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
11 01 2021
11 01 2021
Historique:
received:
18
08
2020
revised:
29
09
2020
pubmed:
6
10
2020
medline:
27
3
2021
entrez:
5
10
2020
Statut:
ppublish
Résumé
Cellular condensation of intrinsically disordered proteins (IDPs) through liquid-liquid phase separation (LLPS) allows dynamic compartmentalization and regulation of biological processes. The IDP tau, which promotes the assembly of microtubules and is hyperphosphorylated in Alzheimer's disease, undergoes LLPS in solution and on the surface of microtubules. Little is known, however, about the influence of tau phosphorylation on its ability to nucleate microtubule bundles in conditions of tau LLPS. Herein, we show that unmodified tau as well as tau phosphorylated at disease-associated epitopes condense into liquid-like droplets. Although tubulin partitioned into and reached high concentrations inside all tau droplets, it was unable to grow into microtubules form the inside of droplets formed by tau phosphorylated at the AT180 epitope (T231/S235). In contrast, neither phosphorylation of tau in the repeat domain nor at its tyrosine residues inhibited the assembly of tubulin from tau droplets. Because LLPS of IDPs has been shown to promote different types of cytoskeletal assembly, our study suggests that IDP phosphorylation might be a broadly used mechanism for the modulation of condensate-mediated cytoskeletal assembly.
Identifiants
pubmed: 33017094
doi: 10.1002/anie.202011157
pmc: PMC7839466
doi:
Substances chimiques
Tubulin
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
726-730Informations de copyright
© 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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