Title

Identification of the Tau phosphorylation pattern that drives its aggregation.

Journal

Proceedings of the National Academy of Sciences of the United States of America

Volume

114

Issue

None

Pages

9080-9085

Date

2017-08-22

Authors

Huvent I | Lippens G | Smet-Nocca C | Qi H | Byrne C | Jacquot Y | Baulieu EE | Cantrelle FX | Chambraud B | Despres C | Landrieu I

Our finding that the resulting Tau species with phosphorylation at Ser202/Th205, but with a disrupted turn-like structure, forms abundant fibers detectable by thioflavin fluorescence or electron microscopy (Figs. 2 and 4) suggests the initial turn-like structure induced by the phosphorylation of only Ser202 and Thr205 is protective against aggregation.

Indeed, Tau phosphorylation at the three positions, Ser202/Thr205/Ser208, while not at Ser262, is sufficient to induce aggregation without the addition of any exogenous aggregation inducer.

Phosphorylation at Ser208 might be catalyzed by Casein kinase 1 (44), and its identification as a potential site for O-GlcNacylation (45) points to the important role of this residue.

When combined with ERK2 catalyzed phosphorylation, the turn-like disrupting G207V mutation in TauF8 hence leads to fast aggregation that already occurs during the phosphorylation reaction.

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