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Comment
. 2022 Sep 1;132(17):e162030.
doi: 10.1172/JCI162030.

Goblet cells need some stress

Malin Ev Johansson, Gunnar C Hansson
Comment

Goblet cells need some stress

Malin Ev Johansson et al. J Clin Invest. .

Abstract

The intestinal tract is protected by epithelium-covering mucus, which is constantly renewed by goblet cells, a specialized type of epithelial cell. Mucus is largely composed of MUC2 mucin, an enormous molecule that poses a high demand on the endoplasmic reticulum (ER) for proper folding and protein assembly, creating a challenge for the secretory machinery in goblet cells. In this issue of the JCI, Grey et al. reveal that the ER resident protein and folding sensor ERN2 (also known as IRE1β) was instrumental for goblet cells to produce sufficient amounts of mucus to form a protective mucus layer. In the absence of ERN2, mucus production was reduced, impairing the mucus barrier, which allowed bacteria to penetrate and cause an epithelial cell stress response. This study emphasizes the importance of a controlled unfolded protein response (UPR) for goblet cell secretion.

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Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1
Figure 1. A model of ER stress response in goblet cells with and without ERN2.
ERN2 is specifically expressed in goblet cells, where it allows for expansion of the ER, which is important for mucus production at homeostasis. In the absence of ERN2, goblet cells fail to produce normal amounts of mucins, resulting in ER mucin accumulation and poor protection of the epithelium. ERN2 controls and dampens the UPR. During enhanced mucus turnover and bacterial stimulation, as in colitis, ER stress and UPR responses are exaggerated and the mucus protection fails.
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