RT Journal Article
SR Electronic
T1 Localization, induction, and cellular effects of tau-phospho-threonine 217
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.18.488657
DO 10.1101/2022.04.18.488657
A1 Binita Rajbanshi
A1 James W. Mandell
A1 George S. Bloom
YR 2022
UL http://biorxiv.org/content/early/2022/04/18/2022.04.18.488657.abstract
AB Introduction Tau phosphorylation at T217 is a promising AD biomarker, but its functional consequences were unknown.Methods Human brain and cultured mouse neurons were analyzed by immunoblotting and immunofluorescence for total tau, taupT217, taupT181, taupT231 and taupS396/pS404. dSTORM super resolution microscopy was used to localize taupT217 in cultured neurons. EGFP-tau was expressed in fibroblasts as wild type and T217E pseudo-phosphorylated tau, and fluorescence recovery after photobleaching (FRAP) reported tau turnover rates on microtubules.Results In brain, taupT217 appears in neurons at Braak stages I-II, becomes more prevalent later and co-localizes partially with other phospho-tau epitopes. In cultured neurons taupT217, is increased by extracellular tau oligomers (xcTauOs), and is associated with developing post-synaptic sites. FRAP recovery was fastest for EGFP-tauT217E.Conclusion TaupT217 increases in brain as AD progresses and is induced by xcTauOs. Post-synaptic taupT217 suggests a role for T217 phosphorylation in synapse impairment. T217 phosphorylation reduces tau’s affinity for microtubules.Competing Interest StatementThe authors have declared no competing interest.