Autophagy controls mucus secretion from intestinal goblet cells by alleviating ER stress

Colonic goblet cells are specialized epithelial cells that secrete mucus to form a barrier between the host and its microbiota, thus preventing bacterial invasion and inflammation. How goblet cells control the amount of mucus they secrete is unclear. We found that constitutive activation of autophagy in mice via Beclin 1 led to production of a thicker and less penetrable mucus layer by reducing endoplasmic reticulum (ER) stress. Accordingly, inhibiting Beclin 1-induced autophagy via Bcl-2 impaired mucus secretion. Furthermore, alleviating intestinal ER stress with a bile acid, or activating the unfolded protein response (UPR) pharmacologically via eIF2α phosphorylation, led to excessive mucus production. Over-production of mucus altered the gut microbiome, with expansion of mucus-utilizing bacteria, and protected from intestinal inflammation. Thus, ER stress is a cell-intrinsic switch that limits mucus secretion, while autophagy maintains proper mucus secretion and intestinal homeostasis by relieving ER stress.

• Publication year

  2022

• Venue

  bioRxiv

• Publication date

  2022-05-28

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1101/2022.05.26.493604PMID 36738733PMCID 10016318
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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