Paired Helical Filament-Forming Region of Tau (297-391) Influences Endogenous Tau Protein and Accumulates in Acidic Compartments in Human Neuronal Cells.

Journal of Molecular Biology
Saskia J PollackLouise C Serpell

Abstract

Assembly of tau protein into paired helical filaments and straight filaments is a key feature of Alzheimer's disease. Aggregation of tau has been implicated in neurodegeneration, cellular toxicity and the propagation, which accompanies disease progression. We have reported previously that a region of tau (297-391), referred to as dGAE, assembles spontaneously in physiological conditions to form paired helical filament-like fibres in vitro in the absence of additives such as heparin. This provides a valuable tool with which to explore the effects of tau in cell culture. Here we have studied the cellular uptake of soluble oligomeric and fibrillar forms of dGAE and examined the downstream consequences of tau internalisation into differentiated SH-SY5Y neuroblastoma cells using fluorescence and electron microscopy alongside structural and biochemical analyses. The assembled dGAE shows more acute cytotoxicity than the soluble, non-aggregated form. Conversely, the soluble form is much more readily internalised and, once within the cell, is able to associate with endogenous tau resulting in increased phosphorylation and aggregation of endogenous tau, which accumulates in lysosomal/endosomal compartments. It appears that soluble oligom...Continue Reading

Citations

Dec 8, 2020·Frontiers in Neurology·Sebastian S OakleyLouise C Serpell
Apr 4, 2021·International Journal of Molecular Sciences·Michael G FriedrichRoger J W Truscott

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Methods Mentioned

BETA
transmission electron microscopy
Protein Assay
X-ray
confocal microscopy
electrophoresis
electron microscopy

Software Mentioned

GraphPad Prism
FIJI
Excel

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