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  High capacity of the endoplasmic reticulum to prevent secretion and aggregation of amyloidogenic proteins

Vincenz-Donnelly, L., Holthusen, H., Körner, R., Hansen, E. C., Presto, J., Johansson, J., et al. (2018). High capacity of the endoplasmic reticulum to prevent secretion and aggregation of amyloidogenic proteins. The EMBO Journal, 37(3), 337-350. doi:10.15252/embj.201695841.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-AF13-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-AF14-5
Genre: Journal Article

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 Creators:
Vincenz-Donnelly, Lisa1, Author              
Holthusen, Hauke1, Author              
Körner, Roman1, Author              
Hansen, Erik C.2, Author
Presto, Jenny2, Author
Johansson, Jan2, Author
Sawarkar, Ritwick2, Author
Hartl, F. Ulrich1, Author              
Hipp, Mark S.1, Author              
Affiliations:
1Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565152              
2external, ou_persistent22              

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Free keywords: NF-KAPPA-B; QUALITY-CONTROL; NEURODEGENERATIVE DISEASES; IDENTIFIES YOS9P; DEGRADATION; OS-9; ER; EXPRESSION; CHAPERONE; PATHWAYBiochemistry & Molecular Biology; Cell Biology; endoplasmic reticulum; protein aggregation; proteostasis; quality control;
 Abstract: Protein aggregation is associated with neurodegeneration and various other pathologies. How specific cellular environments modulate the aggregation of disease proteins is not well understood. Here, we investigated how the endoplasmic reticulum (ER) quality control system handles beta-sheet proteins that were designed de novo to form amyloid-like fibrils. While these proteins undergo toxic aggregation in the cytosol, we find that targeting them to the ER (ER-beta) strongly reduces their toxicity. ER-beta is retained within the ER in a soluble, polymeric state, despite reaching very high concentrations exceeding those of ER-resident molecular chaperones. ER-beta is not removed by ER-associated degradation (ERAD) but interferes with ERAD of other proteins. These findings demonstrate a remarkable capacity of the ER to prevent the formation of insoluble beta-aggregates and the secretion of potentially toxic protein species. Our results also suggest a generic mechanism by which proteins with exposed b-sheet structure in the ER interfere with proteostasis.

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Language(s): eng - English
 Dates: 2017-12-152018-02-01
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: ISI: 000423831400002
DOI: 10.15252/embj.201695841
 Degree: -

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Project name : FP7 GA ERC‐2012‐SyG_318987–ToPAG
Grant ID : 318987
Funding program : Funding Programme 7 (FP7)
Funding organization : European Commission (EC)

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Title: The EMBO Journal
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 37 (3) Sequence Number: - Start / End Page: 337 - 350 Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061_1