Increased G3BP2-Tau interaction in tauopathies is a natural defense against Tau aggregation.
Alzheimer’s disease
G3BP2
RBP
Tau aggregation
tauopathies
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
06 09 2023
06 09 2023
Historique:
received:
16
08
2022
revised:
21
02
2023
accepted:
31
05
2023
medline:
11
9
2023
pubmed:
30
6
2023
entrez:
29
6
2023
Statut:
ppublish
Résumé
Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple tauopathies, and it is independent of neurofibrillary tangle (NFT) formation in Alzheimer's disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we found that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in tauopathies.
Identifiants
pubmed: 37385246
pii: S0896-6273(23)00434-8
doi: 10.1016/j.neuron.2023.05.033
pii:
doi:
Substances chimiques
tau Proteins
0
RNA-Binding Proteins
0
G3BP2 protein, human
0
Adaptor Proteins, Signal Transducing
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2660-2674.e9Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests C.W., M.T., N.J.P., T.D., M.E., S.T., L.F., A.B., R.J., and F.G. are employed by F. Hoffmann-La Roche. Parts of the work in this study have been filed in the patent PCT/EP2023/056281.