TY - JOUR T1 - Nuclear Tau modulates VGluT1 expression: a new function for Tau JF - bioRxiv DO - 10.1101/394312 SP - 394312 AU - Giacomo Siano AU - Martina Varisco AU - Maria Claudia Caiazza AU - Valentina Quercioli AU - Marco Mainardi AU - Chiara Ippolito AU - Antonino Cattaneo AU - Cristina Di Primio Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/08/17/394312.abstract N2 - SummaryTau 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 transmission. 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. ER -