10.1021/acs.analchem.5b04509.s002
Waltraud Mair
Waltraud
Mair
Jan Muntel
Jan
Muntel
Katharina Tepper
Katharina
Tepper
Shaojun Tang
Shaojun
Tang
Jacek Biernat
Jacek
Biernat
William W. Seeley
William W.
Seeley
Kenneth
S. Kosik
Kenneth
S.
Kosik
Eckhard Mandelkow
Eckhard
Mandelkow
Hanno Steen
Hanno
Steen
Judith A. Steen
Judith A.
Steen
FLEXITau: Quantifying Post-translational Modifications
of Tau Protein <i>in Vitro</i> and in Human Disease
American Chemical Society
2016
novel therapeutics
site occupancies
protein tau
assay
measure phosphorylation stoichiometry
Tau Protein
tau PTM landscape
tau pathology
Human Disease Tauopathies
AD pathology
FLEXITau
20 phosphorylations
2016-02-15 00:00:00
Dataset
https://acs.figshare.com/articles/dataset/FLEXITau_Quantifying_Post_translational_Modifications_of_Tau_Protein_i_in_Vitro_i_and_in_Human_Disease/3085372
Tauopathies,
including Alzheimer’s disease (AD), are associated
with the aggregation of modified microtubule associated protein tau.
This pathological state of tau is often referred to as “hyperphosphorylated”.
Due to limitations in technology, an accurate quantitative description
of this state is lacking. Here, a mass spectrometry-based assay, FLEXITau,
is presented to measure phosphorylation stoichiometry and provide
an unbiased quantitative view of the tau post-translational modification
(PTM) landscape. The power of this assay is demonstrated by measuring
the state of hyperphosphorylation from tau in a cellular model for
AD pathology, mapping, and calculating site occupancies for over 20
phosphorylations. We further employ FLEXITau to define the tau PTM
landscape present in AD post-mortem brain. As shown in this study,
the application of this assay provides mechanistic understanding of
tau pathology that could lead to novel therapeutics, and we envision
its further use in prognostic and diagnostic approaches for tauopathies.