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Tau Modulates VGluT1 Expression.

Abstract：

: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_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Siano G,Varisco M,Caiazza MC,Quercioli V,Mainardi M,Ippolito C,Cattaneo A,Di Primio C

doi

10.1016/j.jmb.2019.01.023

subject

Has Abstract

pub_date

2019-02-15 00:00:00

pages

873-884

issue

4

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(19)30032-4

journal_volume

431

pub_type

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