Identification of the Tau Phosphorylation Pattern That Drives Its Aggregation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2017 Aug 9

PMID 28784767

Citations 112

Authors

Clement Despres

Cillian Byrne

Haoling Qi

Francois-Xavier Cantrelle

Isabelle Huvent

Beatrice Chambraud

Etienne-Emile Baulieu

Yves Jacquot

Isabelle Landrieu

Guy Lippens

Caroline Smet-Nocca

Affiliations

Soon will be listed here.

Abstract

Determining the functional relationship between Tau phosphorylation and aggregation has proven a challenge owing to the multiple potential phosphorylation sites and their clustering in the Tau sequence. We use here in vitro kinase assays combined with NMR spectroscopy as an analytical tool to generate well-characterized phosphorylated Tau samples and show that the combined phosphorylation at the Ser202/Thr205/Ser208 sites, together with absence of phosphorylation at the Ser262 site, yields a Tau sample that readily forms fibers, as observed by thioflavin T fluorescence and electron microscopy. On the basis of conformational analysis of synthetic phosphorylated peptides, we show that aggregation of the samples correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205.

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