LAUSR

Goblet cells in the small intestinal crypts contain large numbers of mucin granules that are rapidly discharged to clean bacteria from the crypt. Because acetylcholine released by neuronal and nonneuronal cells controls many aspects of intestinal epithelial function, we used tissue explants and organoids to investigate the response of the small intestinal crypt to cholinergic stimulation. The activation of muscarinic acetylcholine receptors initiated a coordinated and rapid emptying of crypt goblet cells that flushed the crypt contents into the intestinal lumen. Cholinergic stimulation induced an expansion of the granule contents followed by intracellular rupture of the mucin granules. The mucus expanded intracellularly before the rupture of the goblet cell apical membrane and continued to expand after its release into the crypt lumen. The goblet cells recovered from membrane rupture and replenished their stores of mucin granules. Mucus secretion from the goblet cells depended on Ca2+ signaling and the expansion of the mucus in the crypt depended on gap junctions and on ion and water transport by enterocytes adjacent to the goblet cells. This distinctive mode of mucus secretion, which we refer to as “expanding secretion,” efficiently cleans the small intestine crypt through coordinated mucus, ion, and fluid secretion by goblet cells and enterocytes. Description Coordination of mucus secretion with ion transport drives small intestinal crypt flushing. Purging the crypt Although bacteria can penetrate the mucus of the small intestine, the crypts remain sterile due to the continuous secretion of mucus and antimicrobial factors from the epithelium. Acetylcholine contributes to many aspects of intestinal epithelial function, including mucus secretion by goblet cells. Using ileal explants and organoids, Dolan et al. found that cholinergic stimulation elicited a distinctive form of secretion characterized by loss of mucus granule integrity, intracellular mucus swelling, and rupture of the plasma membrane of goblet cells. Gap junctions and ion transport by adjacent enterocytes coordinated the release of mucus with that of fluid into the crypt, leading to further expansion of the mucus and flushing of the crypt. These findings identify a unique type of mass secretion event (see the Focus by Weigert) that purges the crypt and likely contributes to the maintenance of crypt sterility.