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Composition and functional role of the mucus layers in the intestine

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Abstract

In discussions on intestinal protection, the protective capacity of mucus has not been very much considered. The progress in the last years in understanding the molecular nature of mucins, the main building blocks of mucus, has, however, changed this. The intestinal enterocytes have their apical surfaces covered by transmembrane mucins and the whole intestinal surface is further covered by mucus, built around the gel-forming mucin MUC2. The mucus of the small intestine has only one layer, whereas the large intestine has a two-layered mucus where the inner, attached layer has a protective function for the intestine, as it is impermeable to the luminal bacteria.

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References

  1. Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC (2008) The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci USA 105:15064–15069

    Article  PubMed  CAS  Google Scholar 

  2. Gill N, Wlodarska M, Finlay BB (2010) The future of mucosal immunology: studying an integrated system-wide organ. Nat Immunol 11:558–560

    Article  PubMed  CAS  Google Scholar 

  3. Lang T, Hansson GC, Samuelsson T (2007) Gel-forming mucins appeared early in metazoan evolution. Proc Natl Acad Sci USA 104:16209–16214

    Article  PubMed  CAS  Google Scholar 

  4. Lang T, Alexandersson M, Hansson GC, Samuelsson T (2004) Bioinformatic identification of polymerizing and transmembrane mucins in the puffer fish Fugu rubripes. Glycobiology 14:521–527

    Article  PubMed  CAS  Google Scholar 

  5. Vinall LE, King M, Novelli M, Green CA, Daniels G, Hilkens J, Sarner M, Swallow DM (2002) Altered expression and allelic association of the hypervariable membrane mucin MUC1 in Helicobacter pylori gastritis. Gastroenterology 123:41–49

    Article  PubMed  CAS  Google Scholar 

  6. Axelsson MA, Karlsson NG, Steel DM, Ouwendijk J, Nilsson T, Hansson GC (2001) Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins. Glycobiology 11:633–644

    Article  PubMed  CAS  Google Scholar 

  7. Olson FJ, Johansson ME, Klinga-Levan K, Bouhours D, Enerbäck L, Hansson GC, Karlsson NG (2002) Blood group A glycosyltransferase occurring as alleles with high sequence difference is transiently induced during a Nippostrongylus brasiliensis parasite infection. J Biol Chem 277:15044–15052

    Article  PubMed  CAS  Google Scholar 

  8. Holmén JM, Olson FJ, Karlsson H, Hansson GC (2002) Two glycosylation alterations of mouse intestinal mucins due to infection caused by the parasite Nippostrongylus brasiliensis. Glycoconj J 19:67–75

    Article  PubMed  Google Scholar 

  9. Atuma C, Strugala V, Allen A, Holm L (2001) The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol Gastrointest Liver Physiol 280:G922–G929

    PubMed  CAS  Google Scholar 

  10. Sheng YH, Lourie R, Linden SK, Jeffery PL, Roche D, Tran TV, Png CW, Waterhouse N, Sutton P, Florin TH, McGuckin MA (2011) The MUC13 cell-surface mucin protects against intestinal inflammation by inhibiting epithelial cell apoptosis. Gut. on-line

  11. Carlstedt I, Herrmann A, Karlsson H, Sheehan J, Fransson LA, Hansson GC (1993) Characterization of two different glycosylated domains from the insoluble mucin complex of rat small intestine. J Biol Chem 268:18771–18781

    PubMed  CAS  Google Scholar 

  12. Macao B, Johansson DG, Hansson GC, Härd T (2006) Autoproteolysis coupled to protein folding in the SEA domain of the membrane-bound MUC1 mucin. Nat Struct Mol Biol 13:71–76

    Article  PubMed  CAS  Google Scholar 

  13. Malmberg EK, Pelaseyed T, Petersson AC, Seidler UE, De Jonge H, Riordan JR, Hansson GC (2008) The C-terminus of the transmembrane mucin MUC17 binds to the scaffold protein PDZK1 that stably localizes it to the enterocyte apical membrane in the small intestine. Biochem J 410:283–289

    Article  PubMed  CAS  Google Scholar 

  14. Pelaseyed T, Hansson GC (2011) CFTR anion channel modulates expression of human transmembrane mucin MUC3 via the PDZ protein GOPC. J Cell Sci 124:3074–3083

    Article  PubMed  Google Scholar 

  15. Lamprecht G, Seidler U (2006) The emerging role of PDZ adapter proteins for regulation of intestinal ion transport. Am J Physiol Gastrointest Liver Physiol 291:G766–G777

    Article  PubMed  CAS  Google Scholar 

  16. Park SW, Zhen G, Verhaeghe C, Nakagami Y, Nguyenvu LT, Barczak AJ, Killeen N, Erle DJ (2009) The protein disulfide isomerase AGR2 is essential for production of intestinal mucus. Proc Natl Acad Sci USA 106:6950–6955

    Article  PubMed  CAS  Google Scholar 

  17. Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS (2008) XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134:743–756

    Article  PubMed  CAS  Google Scholar 

  18. Godl K, Johansson ME, Lidell ME, Mörgelin M, Karlsson H, Olson FJ, Gum JR Jr, Kim YS, Hansson GC (2002) The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment. J Biol Chem 277:47248–47256

    Article  PubMed  CAS  Google Scholar 

  19. Herrmann A, Davies JR, Lindell G, Martensson S, Packer NH, Swallow DM, Carlstedt I (1999) Studies on the “insoluble” glycoprotein complex from human colon. Identification of reduction-insensitive MUC2 oligomers and C-terminal cleavage. J Biol Chem 274:15828–15836

    Article  PubMed  CAS  Google Scholar 

  20. Axelsson MA, Asker N, Hansson GC (1998) O-glycosylated MUC2 monomer and dimer from LS 174T cells are water-soluble, whereas larger MUC2 species formed early during biosynthesis are insoluble and contain nonreducible intermolecular bonds. J Biol Chem 273:18864–18870

    Article  PubMed  CAS  Google Scholar 

  21. Ambort D, van der Post S, Johansson ME, Mackenzie J, Thomsson E, Krengel U, Hansson G (2011) Function of the CysD domain of the gel-forming MUC2 mucin. Biochem J 436:61–70

    Article  PubMed  CAS  Google Scholar 

  22. Johansson ME, Thomsson KA, Hansson GC (2009) Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein. J Proteome Res 8:3549–3557

    Article  PubMed  CAS  Google Scholar 

  23. Lidell ME, Johansson ME, Hansson GC (2003) An autocatalytic cleavage in the C terminus of the human MUC2 mucin occurs at the low pH of the late secretory pathway. J Biol Chem 278:13944–13951

    Article  PubMed  CAS  Google Scholar 

  24. Zhuo L, Hascall VC, Kimata K (2004) Inter-alpha-trypsin inhibitor, a covalent protein–glycosaminoglycan–protein complex. J Biol Chem 279:38079–38082

    Article  PubMed  CAS  Google Scholar 

  25. Johansson ME, Larsson JM, Hansson GC (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci USA 108:4659–4665

    Article  PubMed  CAS  Google Scholar 

  26. Subramani DB, Johansson MEV, Dahlén G, Hansson GC (2010) Lactobacillus and Bifidobacterium species do not secrete proteases that can cleave the MUC2 mucin protein core which organizes the colon mucus layers. Beneficial Microbes 1:343–350

    Article  PubMed  CAS  Google Scholar 

  27. Velcich A, Yang W, Heyer J, Fragale A, Nicholas C, Viani S, Kucherlapati R, Lipkin M, Yang K, Augenlicht L (2002) Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295:1726–1729

    Article  PubMed  CAS  Google Scholar 

  28. Van der Sluis M, De Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB, Buller HA, Dekker J, Van Seuningen I, Renes IB, Einerhand AW (2006) Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131:117–129

    Article  PubMed  Google Scholar 

  29. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102:11070–11075

    Article  PubMed  CAS  Google Scholar 

  30. Gagneux P, Varki A (1999) Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology 9:747–755

    Article  PubMed  CAS  Google Scholar 

  31. Hansson GC (1988) Structural aspects of blood group glycosphingolipids in the gastrointestinal tract. Adv Exp Med Biol 228:465–494

    Article  PubMed  CAS  Google Scholar 

  32. Larsson JM, Karlsson H, Sjovall H, Hansson GC (2009) A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. Glycobiology 19:756–766

    Article  PubMed  Google Scholar 

  33. Larsson JM, Karlsson H, Crespo JG, Johansson ME, Eklund L, Sjövall H, Hansson GC (2011) Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm Bowel Dis. on-line

  34. Xu J, Bjursell MK, Himrod J, Deng S, Carmichael LK, Chiang HC, Hooper LV, Gordon JI (2003) A genomic view of the human–Bacteroides thetaiotaomicron symbiosis. Science 299:2074–2076

    Article  PubMed  CAS  Google Scholar 

  35. Fu J, Wei B, Wen T, Johansson ME, Liu X, Bradford E, Thomsson KA, McGee S, Mansour L, Tong M, McDaniel JM, Sferra TJ, Turner JR, Chen H, Hansson GC, Braun J, Xia L (2011) Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice. J Clin Invest 121:1657–1666

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Swedish Research Council (no. 7461, 21027, and 342-2004-4434), The Swedish Cancer Foundation, The Knut and Alice Wallenberg Foundation (KAW2007.0118), IngaBritt and Arne Lundberg Foundation, Sahlgren’s University Hospital (LUA-ALF), EU-FP7 IBDase (no. 200931), Wilhelm and Martina Lundgren’s Foundation, Torsten och Ragnar Söderbergs Stiftelser, The Sahlgrenska Academy Foundations, and The Swedish Foundation for Strategic Research—The Mucosal Immunobiology and Vaccine Center (MIVAC) and the Mucus-Bacteria-Colitis Center (MBC) of the Innate Immunity Program (2010-2014). We also acknowledge the Mammalian Protein Expression Core Facility at the University of Gothenburg.

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Authors and Affiliations

  1. Department Medical Biochemistry, University of Gothenburg, PO Box 440, 405 30, Gothenburg, Sweden

    Malin E. V. Johansson, Daniel Ambort, Thaher Pelaseyed, André Schütte, Jenny K. Gustafsson, Anna Ermund, Durai B. Subramani, Jessica M. Holmén-Larsson, Kristina A. Thomsson, Joakim H. Bergström, Sjoerd van der Post, Ana M. Rodriguez-Piñeiro, Henrik Sjövall, Malin Bäckström & Gunnar C. Hansson

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  1. Malin E. V. Johansson
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  2. Daniel Ambort
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  8. Jessica M. Holmén-Larsson
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Correspondence to Gunnar C. Hansson.

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Johansson, M.E.V., Ambort, D., Pelaseyed, T. et al. Composition and functional role of the mucus layers in the intestine. Cell. Mol. Life Sci. 68, 3635–3641 (2011). https://doi.org/10.1007/s00018-011-0822-3

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  • DOI: https://doi.org/10.1007/s00018-011-0822-3

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