Publications by authors named "Lisa Neidhardt"
Intestinal goblet cells are secretory cells specialized in the production of mucins, and as such are challenged by the need for efficient protein folding. Goblet cells express Inositol-Requiring Enzyme-1β (IRE1β), a unique sensor in the unfolded protein response (UPR), which is part of an adaptive mechanism that regulates the demands of mucin production and secretion. However, how IRE1β activity is tuned to mucus folding load remains unknown.
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- The study investigates how the unfolded protein response (UPR) is regulated in mucin-producing goblet cells, focusing on the IRE1β transducer.
- It was found that replacing the luminal domain of IRE1α with that of IRE1β in CHO cells altered IRE1's activity, highlighting the role of mucin-specific chaperones like AGR2 in regulating this pathway.
- AGR2 repressed IRE1β activity when expressed in a hybrid IRE1β/α context, but when the goblet cell-specific protein MUC2 was present, AGR2's repression was reversed, indicating a complex interaction that is specific to the unique stress conditions of goblet cells.
Article Synopsis
- The study investigates how ER stress influences the activation of IRE1, a key protein in the Unfolded Protein Response (UPR), focusing on the role of the co-chaperone ERdj4 and the chaperone BiP.
- The researchers found that when BiP is loaded onto IRE1α, it represses UPR signaling in CHO cells, indicating a specific mechanism of action.
- Findings suggest a competitive model where decreasing ER stress allows ERdj4 and BiP to bind to IRE1, leading to the suppression of UPR activation and initiating a protective cellular response.
AMPylation is an inactivating modification that alters the activity of the major endoplasmic reticulum (ER) chaperone BiP to match the burden of unfolded proteins. A single ER-localised Fic protein, FICD (HYPE), catalyses both AMPylation and deAMPylation of BiP. However, the basis for the switch in FICD's activity is unknown.
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