Figure 9. Schematic representation of acetylcholine (ACh)-induced mucus secretion and goblet cell-associated antigen passage (GAP) formation in intestinal goblet cells.

In response to exogenous ACh, intestinal goblet cells respond with an accelerated mucus secretory response mediated by muscarinic ACh receptor 1 (mAChR1), and/or induction of fluid-phase bulk endocytosis of secretory granule membrane (GAP formation) mediated by mAChR4 in the small intestine (SI) and mAChR3 in the distal colon. The endocytic vesicles containing luminal fluid-phase cargo are shuttled through the cell for degradation, membrane recycling, and transcytosis to be acquired by lamina proporia mononuclear phagocytes (LP-MNPs). Using separate mAChRs, Ca²⁺ pools and signaling pathways for the processes of ACh-induced GAP formation and ACh-induced mucus secretion allow these processes to occur independently or in parallel within the same goblet cell forming the basis of how goblet cells can differentially regulate when to maintain the mucus barrier and when to deliver luminal substances to the immune system.