Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response.
chronological aging
proteasome
protein aggregation
protein homeostasis
protein interaction assay
protein quality control
toxicity
yeast
Journal
CNS neuroscience & therapeutics
ISSN: 1755-5949
Titre abrégé: CNS Neurosci Ther
Pays: England
ID NLM: 101473265
Informations de publication
Date de publication:
21 Jun 2023
21 Jun 2023
Historique:
revised:
23
05
2023
received:
10
04
2023
accepted:
24
05
2023
medline:
21
6
2023
pubmed:
21
6
2023
entrez:
21
6
2023
Statut:
aheadofprint
Résumé
The primary histological characteristic of Alzheimer's disease is the presence of neurofibrillary tangles, which are large aggregates of tau protein. Aging is the primary risk factor for the development of Alzheimer's disease, however, the underlying causes of tau protein aggregation and toxicity are unclear. Here we investigated tau aggregation and toxicity under the conditions of compromised protein homeostasis. We used heterologous expression of human tau protein in the unicellular eukaryote yeast Saccharomyces cerevisiae with evolutionarily conserved protein quality control pathways and examined tau-dependent toxicity and aggregation using growth assays, fluorescence microscopy, and a split luciferase-based reporter NanoBiT. Tau protein expressed in yeast under mild proteotoxic stress, or in mutants with impaired pathways for proteotoxic stress response, did not lead to synthetic toxicity or the formation of obvious aggregates. Chronologically old cells also did not develop observable tau aggregates. Our examination of tau oligomerization in living cells using NanoBiT reporter suggests that tau does not form significant levels of oligomers under basal conditions or under mild proteotoxic stress. Together our data suggest that human tau protein does not represent a major burden to the protein quality control system in yeast cells.
Sections du résumé
BACKGROUND
BACKGROUND
The primary histological characteristic of Alzheimer's disease is the presence of neurofibrillary tangles, which are large aggregates of tau protein. Aging is the primary risk factor for the development of Alzheimer's disease, however, the underlying causes of tau protein aggregation and toxicity are unclear.
AIMS
OBJECTIVE
Here we investigated tau aggregation and toxicity under the conditions of compromised protein homeostasis.
METHODS
METHODS
We used heterologous expression of human tau protein in the unicellular eukaryote yeast Saccharomyces cerevisiae with evolutionarily conserved protein quality control pathways and examined tau-dependent toxicity and aggregation using growth assays, fluorescence microscopy, and a split luciferase-based reporter NanoBiT.
RESULTS
RESULTS
Tau protein expressed in yeast under mild proteotoxic stress, or in mutants with impaired pathways for proteotoxic stress response, did not lead to synthetic toxicity or the formation of obvious aggregates. Chronologically old cells also did not develop observable tau aggregates. Our examination of tau oligomerization in living cells using NanoBiT reporter suggests that tau does not form significant levels of oligomers under basal conditions or under mild proteotoxic stress.
CONCLUSION
CONCLUSIONS
Together our data suggest that human tau protein does not represent a major burden to the protein quality control system in yeast cells.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Croatian Science Foundation
ID : IP-2019-04-3584
Organisme : Croatian Science Foundation
ID : IP-2014-09-9730
Organisme : Research Cooperability Program of the Croatian Science Foundation
ID : DOK-2021-02-2505
Organisme : Research Cooperability Program of the Croatian Science Foundation
ID : DOK-2018-01-9299
Organisme : Research Cooperability Program of the Croatian Science Foundation
ID : PZS-2019-02-3610
Organisme : EU
Organisme : European Social Fund
Organisme : Operational Program Efficient Human Resources 2014-2020
Organisme : European Regional Development Fund
Organisme : Operational Program Competitiveness and Cohesion
ID : KK.01.1.1.01.0007
Organisme : CoRE-Neuro
Informations de copyright
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.
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