Cell type-specific inositol-requiring enzyme 1 beta (IRE1β) functions in the intestine. (IMAGE)
Caption
The IRE1β paralogue is expressed in intestinal epithelial cells (IECs), accomplishing different roles. In goblet cells, IRE1β tightly regulates mucin 2 (MUC2) expression through Regulated IRE1-Dependent Decay of RNA (RIDD). X-Box-binding protein 1 (XBP1s) can further regulate endoplasmic reticulum (ER) expansion and cell maturation during ER stress to sustain proper mucus production. IRE1β deficiency leads to unfolded MUC2 accumulation and cell dysfunction, impairing mucus production and sensitising cells for bacterial infection. In Paneth cells, IRE1β by itself does not trigger any phenotype; XBP1 splicing or RIDD have not been addressed. Finally, IRE1β in enterocytes can attenuate IRE1α hyperactivation after XBP1 deficiency. In addition, IRE1β regulates microsomal triglyceride transfer protein (MTP) through RIDD; however, its contribution to chylomicron synthesis or function has not been studied. IRE1β deficiency in enterocytes correlates with increased ER stress in the mouse small intestine and colon.
Credit
Claudio Hetz, Juan Francisco Silva-Agüero, Lisa M Ellerby
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License
CC BY-NC