Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption of the Nuclear Lamina, TDP-43 Mislocalization and Cell Death.

ABSTRACT: Tau is a cytosolic protein that has also been observed in the nucleus, where it has multiple proposed functions that are regulated by phosphorylation. However, the mechanism underlying the nuclear import of tau is unclear, as is the contribution of nuclear tau to the pathology of tauopathies. We have previously generated a pathological form of tau, PH-tau (pseudophosphorylation mutants S199E, T212E, T231E, and S262E) that mimics AD pathological behavior in cells, Drosophila, and a mouse model. Here, we demonstrated that PH-tau translocates into the nucleus of transiently transfected HEK-293 cells, but wildtype tau does not. We identified a putative importin binding site in the tau sequence, and showed that disruption of this site prevents tau from entering the nucleus. We further sh

SUBMITTER: Candia RF 

PROVIDER: S-EPMC9113199 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature