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Tau Internalization is Regulated by 6-O Sulfation on Heparan Sulfate Proteoglycans (HSPGs) 1.0.1

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charles.hoyt@scai.fraunhofer.de at 2019-02-27 16:23:14.451997
Authors
Sandra Spalek
Contact
charles.hoyt@scai.fraunhofer.de
License
CC BY 4.0
Copyright
Copyright © 2018 Fraunhofer Institute SCAI, All rights reserved.
Number Nodes
28
Number Edges
63
Number Components
3
Network Density
0.0833333333333333
Average Degree
2.25
Number Citations
1
Number BEL Errors
0

Content Statistics

Network Overlap

The node-based overlap between this network and other networks is calculated as the Szymkiewicz-Simpson coefficient of their respective nodes. Up to the top 10 are shown below.

Network Overlap
Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation v1.0.0 27%
Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways v1.0.1 21%
Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0 14%
Inert and seed-competent tau monomers suggest structural origins of aggregation v1.0.0 12%
Tau in physiology and pathology v1.0.0 11%
Imbalances in the Hsp90 Chaperone Machinery: Implications for Tauopathies v1.0.0 11%
Tau oligomers and tau toxicity in neurodegenerative disease v1.0.0 11%
Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0 11%
Analysis of Isoform-specific Tau Aggregates Suggests a Common Toxic Mechanism Involving Similar Pathological Conformations and Axonal Transport Inhibition v1.0.1 11%
Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition v1.0.0 8%

Sample Edges

a(CHEBI:"chondroitin sulfate") decreases tloc(a(HBP:"Tau isoform F (441 aa)"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Likewise, addition of 2-O-desulfated heparin was able to reduce uptake, whereas 6-O-desulfated heparin or chondroitin sulfate (negative control) were significantly less effective at reducing uptake (Fig. 4a) PubMed:29686391

a(CHEBI:"chondroitin sulfate") causesNoChange tloc(a(HBP:"Tau isoform F (441 aa)"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Chondroitin sulfate and 6-O-desulfated heparin incubation did not reduce the median fluorescence, verifying that 6-O-sulfation is also important for tau internalization ex vivo (Fig. 4d and Supplementary Fig. 3b) PubMed:29686391

a(CHEBI:dynasore) decreases tloc(a(HBP:"Tau isoform F (441 aa)"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Treatment of cells with an inhibitor for DNM2, Dynasore, was also able to reduce uptake of tau (Supplementary Fig. 2 f) PubMed:29686391

a(CHEBI:heparin) association tloc(a(HBP:"Tau isoform F (441 aa)"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

We found that internalization of tau can be efficiently competed by the presence of heparin or HS in the media (Fig. 4a) PubMed:29686391

a(CHEBI:heparin) decreases tloc(a(HBP:"Tau isoform F (441 aa)"), fromLoc(GO:"extracellular region"), toLoc(GO:intracellular)) View Subject | View Object

Consistent with our previous results, incubation with heparin, heparan sulfate, or 2-O-desulfated heparin reduced uptake of tau as quantified by the median 488 fluorescence intensity (Fig. 4d) PubMed:29686391

Sample Nodes

bp(HBP:neurotoxicity)

In-Edges: 6 | Out-Edges: 1 | Explore Neighborhood | Download JSON

bp(GO:endocytosis)

In-Edges: 25 | Out-Edges: 27 | Explore Neighborhood | Download JSON

p(HGNC:CDK4)

In-Edges: 3 | Out-Edges: 1 | Explore Neighborhood | Download JSON

path(MESH:Tauopathies)

In-Edges: 54 | Out-Edges: 33 | Children: 4 | Explore Neighborhood | Download JSON

a(HBP:"Tau fibrils")

In-Edges: 19 | Out-Edges: 3 | Explore Neighborhood | Download JSON

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.