Tau is a PIAS4 target

R GOBBINI; A ATTORRESI; E ARZT; ML BUDZIÑSKI; S SENIN; AC LIBERMAN; C SOKN; B UGO; M ERDOCIA

Mar del Plata

Congreso; XXXIV Reunion Cientifica Anual en Investigación Clínica; 2019

Tau proteins bind strongly to microtubules and are abundant in neurons. In these cells, they play a key role in the modulation of tubulin dynamics and axonal transport, among others. Tau deregulation leads to neurodegenerative diseases known as taupathies which are characterized by the formation of intracellular tau deposits. These aggregates are composed mainly of hyperphosphorylated tau. Hsp90 is a major cellular chaperone that forms large complexes with a variety of co-chaperones like the inmunophilin FKBP51. This complex has been described as a potential enhancer of abnormal tau stability by inhibiting its proteasomal degradation. Our group has described that FKBP51 SUMOylation, which is enhanced by the SUMO E3 ligase PIAS4, is essential in order to interact with Hsp90. Taking this into account, we hypothesize that PIAS4 could regulate tau stability. In this work we used HEK293 and N2a cells overexpressing PIAS4 SUMO ligase and analysed its effect on tau biology by western blot, cicloheximide assay and confocal microscopy of tau BifC dimerization fluorescent biosensor. Our results show that PIAS4 promotes tau and phospho tau accumulation (total tau: 59%, p