When the AGR2 gene is not functioning properly, the number of goblet cells—specialized cells that produce protective mucus in the intestines—drops dramatically in the small intestine and is...
Mechanism
Synthesis from 1 study
Goblet cells make a huge amount of mucus, and AGR2 helps them fold it correctly. Without AGR2, the mucus protein gets stuck and breaks the cell’s internal quality control system. This overload kills only the mucus cells, because other gut cells don’t work as hard — so the gut loses its protective...
Most probable mechanism
Without AGR2, mucus-producing cells in the gut can't properly fold their main mucus protein, causing it to pile up inside the cell. This overload triggers a stress response that the cell can't fix, which eventually kills the mucus cells. Other gut cells don't rely as much on this process, so they survive, leaving the gut without its protective mucus layer.
AGR2 is required for the proper folding and maturation of the MUC2 mucin protein in the endoplasmic reticulum of goblet cells
Loss of AGR2 function causes accumulation of misfolded, non-glycosylated MUC2 precursor in the endoplasmic reticulum
Accumulated misfolded MUC2 overwhelms the endoplasmic reticulum's protein-folding capacity, triggering sustained endoplasmic reticulum stress
AGR2 independently regulates endoplasmic reticulum stress resolution, and its absence prevents normalization of stress markers even in non-mucin-producing cells
Persistent endoplasmic reticulum stress activates apoptotic pathways specifically in goblet cells due to their high protein synthesis load
Goblet cell apoptosis results in near-complete depletion of these cells in the small intestine and severe reduction in the colon
Evidence from Studies
Supporting (1)
Community contributions welcome
Human AGR2 Deficiency Causes Mucus Barrier Dysfunction and Infantile Inflammatory Bowel Disease
Contradicting (0)
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