Proteomics

Dataset Information

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Targeted mass spectrometry of Tau preparations purified from Alzheimer’s Disease brains plus either the deubiquitylase USP21 or its activity-dead mutant C221A.


ABSTRACT: To characterise the abundance of ubiquitylated Tau peptides in the presence of active or inactive variants (wt 196-565 vs. C221A) of the broad spectrum deubiquitylase USP21. Tau peptides are obtained from Tau fibrils purified from post mortem human brains diagnosed with Alzheimer’s. Their detection is facilitated by previous training of the mass spectrometer with in vitro ubiquitylated Tau. The same samples were used to evaluate the percentage of peptides modified with ubiquitin

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Dorothea Anrather  

LAB HEAD: Sascha Martens

PROVIDER: PXD046645 | Pride | 2024-06-18

REPOSITORIES: Pride

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Publications

Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion.

Ferrari Luca L   Bauer Bernd B   Qiu Yue Y   Schuschnig Martina M   Klotz Sigrid S   Anrather Dorothea D   Juretschke Thomas T   Beli Petra P   Gelpi Ellen E   Martens Sascha S  

Science advances 20240612 24


The accumulation of protein aggregates is a hallmark of many diseases, including Alzheimer's disease. As a major pillar of the proteostasis network, autophagy mediates the degradation of protein aggregates. The autophagy cargo receptor p62 recognizes ubiquitin on proteins and cooperates with TAX1BP1 to recruit the autophagy machinery. Paradoxically, protein aggregates are not degraded in various diseases despite p62 association. Here, we reconstituted the recognition by the autophagy receptors o  ...[more]

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