Integration of inositol-requiring enzyme 1 beta (IRE1β) and anterior gradient protein 2 homolog (AGR2) sensing mechanism and adjustment of goblet cell function. (IMAGE)
Caption
AGR2 interacts with IRE1β to disrupt its oligomerisation, thereby blocking its endonuclease activity. On endoplasmic reticulum (ER) stress, AGR2 dissociates to counter mucin 2 (MUC2) unfolding, enabling IRE1β activation and signalling. XBP1s expression allows goblet cell adaptation through ER expansion and possibly by regulating AGR2 gene transcription. Ablation of AGR2 expression in goblet cells induces spontaneous IRE1β hyperactivation, increasing X-Box-binding protein 1 (XBP1) splicing. However, the subsequent cellular effects of XBP1s expression and Regulated IRE1-Dependent Decay of RNA (RIDD) activation in the absence of ER stress have not been addressed. UPR, unfolded protein response.
Credit
By Claudio Hetz, Juan Francisco Silva-Agüero, Lisa M Ellerby
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CC BY-NC