2023年12月18日 · Here, we exploited the beta isoform of the UPR transducer IRE1, that is specific to mucin-producing cells in order to gauge the relative regulatory roles of activating ligands and repressing chaperones of the specialised ER of goblet cells.

2023年12月20日 · We identified the disulfide isomerase and mucin chaperone AGR2 as a goblet cell-specific protein that crucially regulates IRE1β-, but not IRE1α-mediated signaling. AGR2 binding to IRE1β disrupts IRE1β oligomerization, thereby …

2021年6月1日 · Several dedicated molecules with a unique tissue-specific expression in mucosal epithelia govern mucosal homeostasis. Here, we review the biology of Inositol-requiring enzyme 1β (IRE1β), an...

2013年2月19日 · Here, we report that IRE1β plays a distinctive role in mucin-secreting goblet cells. In IRE1β(-/-) mice, aberrant mucin 2 (MUC2) accumulated in the ER of goblet cells, accompanied by ER distension and elevated ER stress signaling such as …

Introduction of the goblet cell-specific client MUC2 reversed AGR2-mediated repression of the IRE1β/α chimera. In vitro, AGR2 actively de-stabilised the IRE1β luminal domain dimer and formed a reversible complex with the inactive monomer.

2024年11月15日 · When large amount of unfolded mucin is produced, it triggers AGR2 dissociation of IRE1β, resulting in IRE1β dimerization and activation. Activation of IRE1β may cleave Mucin 2 (MUC2) mRNA to optimize the efficient folding and secretion of MUC2 and promote endoplasmic reticulum homeostasis [20].

2019年8月1日 · We found T-2 toxin induced endoplasmic reticulum stress and activated the IRE1/XBP1 pathway, which may be related to the inhibition of MUC2. Interestingly, T-2 toxin activated IRE1α to inhibit IRE1β, which optimized mucin production.

2017年1月11日 · IRE1β mRNA expression levels were positively correlated with MUC2 mRNA expression levels. IRE1β expression levels were revealed to be significantly associated with lymph node metastasis, tumor stage and histological differentiation.

Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts.

2013年11月1日 · Moreover, IRE1β −/− mice display a distended ER phenotype, potentially due to overaccumulation of Mucin2 (MUC2), the most prominent protein secreted from goblet cells. This suggests that IRE1β controls MUC2 expression in goblet cells.