engleski

Characterization of human tau protein in yeast cells under normal and stress conditions

Age-dependent protein aggregation is a conserved phenomenon that is associated with many neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by aggregation of Tau, a microtubule-binding protein that is normally soluble and mainly localized to neuronal axons, but can form oligomers and higher-order amyloid-like aggregates that accumulate in soma and dendrites and eventually lead to neuronal death. Although the main risk factor for the onset of AD is aging, the exact causes of Tau protein aggregation are largely unclear. To investigate factors that influence Tau protein aggregation, we expressed human Tau protein fused with fluorescent proteins in yeast Saccharomyces cerevisiae. We examined intracellular localization of Tau in young and aged cells, and in cells under different stress conditions, such as glucose starvation, elevated temperature, hyperosmotic and proteotoxic stress caused by toxic amino acid analogue. Furthermore, to study factors affecting Tau oligomerization, we used luminescent reporter NanoBiT in which protein-protein interaction results in the complementation of the luciferase NanoLuc. Results show basal levels of Tau-NanoBiT reporter signal in logarithmically growing wild-type cells, suggesting that Tau oligomerization doesn't occur under normal growth conditions.

aging ; elevated temperature ; glucose starvation ; hyperosmotic stress ; intracellular localization ; luminescent reporter ; protein-protein interactions ; proteotoxic stress ; tau protein aggregation ; tau protein oligomerization ; stress conditions ; tau protein ; yeast

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