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

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 β-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-β) strongly reduces their toxicity. ER-β is retained within the ER in a soluble, polymeric state, despite reaching very high concentrations exceeding those of ER-resident molecular chaperones. ER-β is not removed by ER-associated degradation (ERAD) but interferes with ERAD of other proteins. These findings demonstrate a remarkable c

SUBMITTER: Vincenz-Donnelly L 

PROVIDER: S-EPMC5793802 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature