Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response

Klara Zubčić, Dina Franić, Mihaela Pravica, Patrick R. Hof, Goran Šimić, Mirta Boban

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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: Here we investigated tau aggregation and toxicity under the conditions of compromised protein homeostasis. 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: 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: Together our data suggest that human tau protein does not represent a major burden to the protein quality control system in yeast cells.

Original languageEnglish
JournalCNS Neuroscience and Therapeutics
DOIs
StateAccepted/In press - 2023

Keywords

  • chronological aging
  • proteasome
  • protein aggregation
  • protein homeostasis
  • protein interaction assay
  • protein quality control
  • toxicity
  • yeast

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