Nuclear Tau modulates VGluT1 expression: a new function for Tau [article]

Giacomo Siano, Martina Varisco, Maria Claudia Caiazza, Valentina Quercioli, Marco Mainardi, Chiara Ippolito, Antonino Cattaneo, Cristina Di Primio
2018 bioRxiv   pre-print
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 DNA-bound fractions. We show that nuclear Tau regulates the expression of VGluT1, a disease-relevant gene directly involved in glutamatergic synaptic
more » ... n. Impeding Tau/tubulin interaction in the cytosol favours its nuclear translocation and increases VGluT1 expression. Remarkably, the P301L mutation 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.
doi:10.1101/394312 fatcat:23sevfx5abhu5i22j3k356rjbu