期刊
EMBO JOURNAL
卷 37, 期 3, 页码 337-350出版社
WILEY
DOI: 10.15252/embj.201695841
关键词
endoplasmic reticulum; protein aggregation; proteostasis; quality control
资金
- Boehringer Ingelheim Fonds
- Max Planck Foundation
- European Commission [FP7 GA ERC-2012-SyG_318987-ToPAG]
- Deutsche Forschungsgemeinschaft (German Research Foundation)
- Max Planck Society
- German Research Foundation (DFG) [SA3190]
- DFG collaborative research center Medical Epigenetics
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据