PubMed: 28784767

Identification of the Tau phosphorylation pattern that drives its aggregation.
Proceedings of the National Academy of Sciences of the United States of America
Huvent I | Lippens G | Smet-Nocca C | Qi H | Byrne C | Jacquot Y | Baulieu EE | Cantrelle FX | Chambraud B | Despres C | Landrieu I

Evidence d42dae3c7f

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.

Evidence 6a0011c5d6

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.

Evidence 831e912412

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.

Evidence 60964a5972

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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