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bioRxiv · 10.1101/2022.04.18.488657

Localization, induction, and cellular effects of tau-phospho-threonine 217

Rajbanshi, B.·Mandell, J. W.·Bloom, G. S.
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Abstract

IntroductionTau phosphorylation at T217 is a promising AD biomarker, but its functional consequences were unknown. MethodsHuman 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. ResultsIn 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. ConclusionTaupT217 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 taus affinity for microtubules.

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Rajbanshi, B., Mandell, J. W., Bloom, G. S.. 2022-04-18. Localization, induction, and cellular effects of tau-phospho-threonine 217. https://doi.org/10.1101/2022.04.18.488657

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