FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease

被引：94

作者：

Mair, Waltraud ^{[1
,2
]}

Muntel, Jan ^{[3
,4
,10
]}

Tepper, Katharina

Tang, Shaojun ^{[3
,4
,11
,12
]}

Biernat, Jacek ^{[5
]}

Seeley, William W. ^{[7
,8
]}

Kosik, Kenneth S. ^{[9
]}

Mandelkow, Eckhard ^{[6
]}

Steen, Hanno ^{[3
,4
]}

Steen, Judith A. ^{[1
,2
]}

机构：

[1] Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA

[3] Boston Childrens Hosp, Pathol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Pathol, Boston, MA 02115 USA

[5] German Ctr Neurodegenerat Dis, DZNE, D-53175 Bonn, Germany

[6] Ctr Adv European Studies & Res, CAESAR, D-53175 Bonn, Germany

[7] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94158 USA

[8] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA

[9] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA

[10] Biognosys AG, CH-8952 Schlieren, Switzerland

[11] Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC 20057 USA

[12] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA

来源：

ANALYTICAL CHEMISTRY | 2016年 / 88卷 / 07期

基金：

美国国家卫生研究院;

关键词：

DOWN MASS-SPECTROMETRY; HELICAL FILAMENT-TAU; ALZHEIMERS-DISEASE; PHOSPHORYLATION SITES; ABNORMAL PHOSPHORYLATION; BRAIN; ACETYLATION; REPRODUCIBILITY; QUANTIFICATION; GLYCOSYLATION;

D O I：

10.1021/acs.analchem.5b04509

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

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 phosphorylation. 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.

引用

页码：3704 / 3714

页数：11

共 43 条

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