Tau displacement from microtubules is the first step in the onset of tauopathies and is followed by toxic protein aggregation. However, other non-canonical functions of Tau might have a role in these pathologies. Here, we demonstrate that a small amount of Tau localizes in the nuclear compartment and accumulates in both the soluble and chromatin-bound fractions. We show that favoring Tau nuclear translocation and accumulation, by Tau overexpression or detachment from MTs, increases the expression of VGluT1, a disease-relevant gene directly involved in glutamatergic synaptic transmission. Remarkably, the P301L mutation, related to frontotemporal dementia FTDP-17, impairs this mechanism leading to a loss of function. Altogether, our results provide the demonstration of a direct physiological role of Tau on gene expression. Alterations of this mechanism may be at the basis of the onset of neurodegeneration.
Journal article
2019-02-15T00:00:00+00:00
431
873 - 884
11
Tau, Tau P301L, VGluT1, gene expression, nuclear tau, Cell Line, Cell Line, Tumor, Chromatin, Gene Expression, HeLa Cells, Humans, Microtubules, Mutation, Tauopathies, Vesicular Glutamate Transport Protein 1, tau Proteins