Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mass spectrometry analysis of in vitro Tau ubiquitination by the UBA1/Hsp70/CHIP machinery

ABSTRACT: We aimed at characterizing which lysines on Tau were ubiquitinated by the UBA1/Hsp70/CHIP machinery. We also determined the ubiquitin linkages of the assembled Tau chains.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Alzheimer's Disease

SUBMITTER: Dorothea Anrather

LAB HEAD: Sascha Martens

PROVIDER: PXD034527 | Pride | 2024-06-18

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20210622_E3_RSLC6_Ferrari_Martens_MPL_5B1_band1_50p.raw	Raw
	20210622_E3_RSLC6_Ferrari_Martens_MPL_5B1_band2_50p.raw	Raw
	20210622_E3_RSLC6_Ferrari_Martens_MPL_5B1_band3_50p.raw	Raw
	20210622_E3_RSLC6_Ferrari_Martens_MPL_5B1_band4_50p.raw	Raw
	20210622_E3_RSLC6_Ferrari_Martens_MPL_5B1_band5_50p.raw	Raw

Items per page:

1 - 5 of 26

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]

PMID: 38865459

Similar Datasets

Combinatorial native MS and LC-MS/MS approach reveals high intrinsic phosphorylation of human Tau

Project description:Abnormal changes in the neuronal microtubule-associated protein Tau, such as high phosphorylation and aggregation, are considered hallmarks of cognitive deficits in Alzheimer disease. Abnormal phosphorylation is thought to take place before aggregation, and therefore it is often assumed that phosphorylation predisposes Tau towards aggregation. However, the nature and extent of phosphorylation has remained ill-defined. Tau protein contains up to 85 potential phosphorylation sites (80 Ser/Thr, and 5 Tyr P-sites), many of which can be phosphorylated by various kinases because the unfolded structure of Tau makes them accessible. However, limitations in methods (e.g. in mass spectrometry of phosphorylated peptides, or antibodies against phospho-epitopes) have led to conflicting results regarding the overall degree of phosphorylation of Tau in cells. Here we present results from a new approach, that is based on native mass spectrometry analysis of intact Tau expressed in a eukaryotic cell system (Sf9) which reveals Tau in different phosphorylation states. The extent of phosphorylation is remarkably heterogeneous with up to ~20 phosphates (Pi) per molecule and distributed over 51 sites (including all P-sites published so far and additional 18 P-sites). The medium phosphorylated fraction Pm showed overall occupancies centered at 8 Pi (± 5 Pi) with a bell-shaped distribution, the highly phosphorylated fraction Ph had 14 Pi (± 6 Pi). The distribution of sites was remarkably asymmetric (with 71% of all P-sites located in the C-terminal half of Tau). All phosphorylation sites were on Ser or Thr residues, but none on Tyr. Other known posttranslational modifications of Tau were near or below our detection limit (e.g. acetylation, ubiquitination).

2020-11-20 | PXD020985 | Pride

Mouse gestational protein restriction: Newborn offspring liver and hindleg muscle

Project description:Gestational protein restriction is a model for low birth size. We hypothesized that taurine supplementation would protect against changes in newborn liver and muscle caused by a maternal low protein diet. Pregnant mouse dams were subjected to different diet schemes from day 1 of pregnancy until birth. Pups were killed following birth and liver and hindleg skeletal muscle taken out and frozen at -80C until analysis. Diet schemes: Normal Protein (20% casein; NP), Normal Protein + taurine (1% taurine supplementation in water ad libitum; NP+tau), Low Protein (8% casein; LP) and LP+tau The liver and muscle samples were normalized separately.

2009-11-07 | E-GEOD-12730 | biostudies-arrayexpress

Quantitative PTM Maps of Human Pathologic Tau Identify Patient Heterogeneity and Define Critical Steps in Alzheimer’s Disease Progression - angular gyrus

Project description:To elucidate the role of Tau isoforms and PTM stoichiometry in Alzheimer’s disease (AD), we generated a high resolution quantitative proteomic map of 88 PTMs on multiple isoforms of Tau isolated from the post-mortem human tissue from 49 AD and 42 control subjects. While Tau PTM maps reveal heterogeneity across subjects, a subset of PTMs display high occupancy and patient frequency for AD suggesting importance in disease. Unsupervised analyses indicate that PTMs occur in an ordered manner leading to Tau aggregation. The processive addition and minimal set of PTMs associated with seeding activity was further defined by the analysis of size fractionated Tau. To summarize, critical features within the Tau protein for disease intervention at different stages of disease are identified, including enrichment of 0N and 4R isoforms, underrepresentation of the C-terminal, an increase in negative charge in the PRR and a decrease in positive charge in the MBD.

2020-12-04 | PXD020517 | Pride

Cancer-specific association between Tau (MAPT) and cellular pathways, clinical outcome, and drug response

Project description:Tau (MAPT) is a microtubule-associated protein causing frequent neurodegenerative diseases or inherited frontotemporal lobar degenerations. Emerging evidence for non-canonical functions of Tau in DNA protection and P53 regulation suggests its involvement in cancer. Indeed, Tau expression correlates with cancer-specific survival or response to microtubule therapeutics. These data may imply common molecular pathways involved in the pathogenesis of neurodegenerative disorders and cancer. To bring new evidence that Tau represents a key protein in cancer, we present an in silico pan-cancer analysis of MAPT transcriptomic profile in over 11000 clinical samples and over 1300 pre-clinical samples provided by the TCGA and the DEPMAP datasets respectively. We completed this analysis by exploring a possible interplay of MAPT with wild-type or mutated P53. Then, we calculated the impact of MAPT expression on clinical outcome and drug response. Overall, the results support a relevant role of the MAPT gene in several cancer types, although the contribution of Tau to cancer appears to very much depend on the cellular context.

2022-11-27 | E-MTAB-8166 | biostudies-arrayexpress

Quantitative PTM Maps of Human Pathologic Tau Identify Patient Heterogeneity and Define Critical Steps in Alzheimer’s Disease Progression - MC1-isolated Tau

2020-12-04 | PXD020482 | Pride

Specific post-translational modifications of the soluble tau protein distinguish between Alzheimer’s disease, 4R-, and 3R-tauopathies

Project description:The tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The type of tau isoforms (4R/3R) observed in brain aggregates is used to classify tauopathies. However, distinguishing tauopathies in cerebrospinal fluid remains challenging. Here, we demonstrated that the difference in tau isoforms between tauopathies is only observed in aggregates, not in soluble brain extracts. We therefore used untargeted mass spectrometry to characterize all post-translational modifications of both the aggregated and the soluble tau protein obtained from human brain tissue of patients with Alzheimer’s disease, cortico-basal degeneration, Pick’s disease, and fronto-temporal lobe degeneration. We found specific soluble signatures predictive of each tauopathy and its peculiar type of aggregated tau isoforms. These findings provide potential targets for developing cerebrospinal fluid assays able to distinguish between tauopathies in vivo. The comparison between soluble and aggregated tau features indicates potential mechanisms of tau aggregation, providing novel therapeutic leads for these diseases

2023-06-22 | PXD038901 | Pride

Whole genome gene expression analysis of a genomic mouse model of tauopathy

Project description:The goal of this study was to assess the number and types of differentially expressed genes in a transgenic (genomic) mouse model of tau pathology. Notably, we crossed previously described genomic mouse line called â8câ that expresses all isoforms of human tau protein (Duff et al., Neurobiology of Disease, 2000;7(2):87) with a mouse tau knockout line (Dawson et al., J Cell Sci 2001;114:1179) and generated humanized mice line called âhTau Dk/Dkâ. These mice are complete knockout of endogenous mouse tau and express all six isoforms of human tau driven by the endogenous human tau promoter. We performed microarray analysis in the hippocampal tissue from six-month old hTau Dk/Dk mice (n=3) and compared it with age-matched non-transgenic control group. Both the lines are in C57BL/6J genetic background.

2017-03-15 | E-MTAB-5078 | biostudies-arrayexpress

Quantitative PTM Maps of Human Pathologic Tau Identify Patient Heterogeneity and Define Critical Steps in Alzheimer’s Disease Progression - high/low molecular weight tau

2020-12-04 | PXD020483 | Pride

A pilot study for deciphering post-translational modifications and proteoforms of tau protein by capillary electrophoresis-mass spectrometry

Project description:Abnormal accumulation of tau proteins is one pathological hallmark of Alzheimer’s disease (AD). Many tau protein post-translational modifications (PTMs) are associated with the development of AD, such as phosphorylation, acetylation, and methylation. Therefore, a complete picture of PTM landscape of tau is critical for understanding the molecular mechanisms of AD progression. Here, we offered a pilot study of combining two complementary analytical techniques, capillary zone electrophoresis (CZE)-tandem mass spectrometry (MS/MS) and reversed-phase liquid chromatography (RPLC)-MS/MS, for bottom-up proteomics of tau-0N3R. We identified 53 phosphorylation sites of tau-0N3R in total, which is about 30% higher than that from RPLC-MS/MS alone. CZE-MS/MS provided more PTM sites (i.e., phosphorylation) and modified peptides of tau-0N3R than RPLC-MS/MS, and its predicted electrophoretic mobility helped improve the confidence of the identified modified peptides. We developed a highly efficient capillary isoelectric focusing (cIEF)-MS technique to offer a bird’s-eye view of tau-0N3R proteoforms, with 11 putative tau-0N3R proteoforms carrying up to ten phosphorylation sites and lower pI values from more phosphorylated proteoforms detected. Interestingly, under a native-like cIEF-MS condition, we observed three putative tau-0N3R dimers carrying phosphate groups. The findings demonstrate that CE-MS is a valuable analytical technique for the characterization of tau PTMs, proteoforms, and even oligomerization.

2024-10-15 | PXD053367 | Pride

Insight into the structure of the “unstructured” tau protein

Project description:Here, we apply a recently-developed approach for de novo protein structure determination based on the incorporation of short-distance crosslinking data as constraints in discrete molecular dynamics simulations (CL-DMD), for the determination of the conformational ensemble of tau protein in solution. The predicted structure may facilitate an understanding of the misfolding and oligomerization pathways of the tau protein.

2019-10-08 | PXD015044 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data