Goblet cells & Mucus

The organization of the glycosylation machinery within the Goblet cell is depicted (1).

N-Glycans Support MUC2 Folding and Secretion

N-glycan addition in goblet cells is crucial for proper MUCIN-2 (MUC2) production because it ensures correct mucin folding, maturation, and secretion. Without N-glycans, MUCIN-2 (MUC2) cannot form the necessary dimers and oligomers, which are critical for its function as a gel-forming mucin (2, 3).

O-Glycosylation Builds the Mucin Carbohydrate Layer

O-glycosylation initiation means the addition of N-acetylgalactosamine (GalNAc) to the protein backbone, followed by elongation with galactose and N-acetylglucosamine, followed by termination through addition of sialic acid (i.e., Neu5Ac / N-Acetylneuraminic acid) and fucose (1, 4).

Neural and Immune Signals Regulate Goblet Cells

Neuronal and immunological factors help in the formation of new goblet cells and also trigger mucus secretion (5, 6).

Goblet Cells Secrete MUC2 to Protect the Gut

-=- Goblet cells secrete mucin for the mucus layer that shields the intestinal epithelial cells (IECs) from luminal bacteria (7, 8). An intercrypt subpopulation of goblet cells is primarily responsible for mucus secretion, predominantly mucin-2 (MUC2), to inhibit pathogen invasion (9, 10) and support essential colonic mucus barrier function (11). However, In mouse and human cell lines, insufficient butyrate can cause the mucin-producing goblet cells to switch from beta-oxidation to anaerobic glycolysis, which negatively affects goblet cell differentiation and the synthesis of MUC2 (10).

References

(1) Luis & Hansson 2023 Cell Host & Microbe 31(7):
(2) Sun et al. 2023 Molecules 28: 7033
(3) Roy et al. 2025 Res Sq [Preprint] rs.3.rs-6222474
(4) Marth 2022 in: Varki et al. 2022 (editors) Essentials of Glycobiology 4th edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press
(5) Schwerdtfeger & Tobet 2020 Physiol Rep 8(3): e14363
(6) Yang et al. 2022f Cell 185(22): 4190-4205
(7) Gerbe et al. 2012 Cell Mol Life Sci. 69: 2907-2917
(8) Pelaseyed et al. 2014 Immunol. Rev. 260: 8-20
(9) Min & Rhee, 2015
(10) Wolter et al. 2021 Nat Rev Gastroenterol Hepatol 18(12): 885-902
(11) Nyström et al. 2021 Science 372: eabb1590

see also:
Helminth Infections / Helminthiasis & Tuft Cells
Intestinal Mucosal Barrier / Mucus Layer & Composition
Sialic acids