Comparative interactome analyses of wild-type and P301L MAPT in two human neuronal cell lines

Protein interactions of the tau protein are of interest in efforts to decipher the mechanisms of cell death in Alzheimer Disease (AD), a subset of frontotemporal dementias (FTD) and other tauopathies. We recently reported on extensive interactions of tau with the ribonucleoproteome and chaperones. A confounder of this prior work was that it probed steady-state interactions of plasmid-encoded four-repeat (4R) tau in dividing cells. Since then, we genome-edited a genomic safe harbor locus in two human neuronal cell lines, namely IMR-32 and ReNcell VM, creating inducible EGFP tagged wild-type and P301L tau models. We expressed balanced levels of 3R- and 4R-tau and interrogated tau protein interactions at specific times following its induction. In addition to its association with the ribonucleoproteome, tau was observed to interact in these models with proteins that escaped prior investigations.