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Tau Modulates VGluT1 Expression
- Siano, Giacomo, Varisco, Martina, Caiazza, Maria Claudia, Quercioli, Valentina, Mainardi, Marco, Ippolito, Chiara, Cattaneo, Antonino, Di Primio, Cristina
- Journal of molecular biology 2019 v.431 no.4 pp. 873-884
- dementia, gene overexpression, genes, microtubules, mutation, neurodegenerative diseases, synaptic transmission
- 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.