| First Author | Schütte A | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 34 | Pages | 12396-401 |
| PubMed ID | 25114233 | Mgi Jnum | J:214078 |
| Mgi Id | MGI:5588039 | Doi | 10.1073/pnas.1407597111 |
| Citation | Schutte A, et al. (2014) Microbial-induced meprin beta cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus. Proc Natl Acad Sci U S A 111(34):12396-401 |
| abstractText | The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel-forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a two-layered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin beta-deficient mice was now found to be attached. Meprin beta is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin beta was added to the attached mucus of meprin beta-deficient mice, the mucus was detached from the epithelium. Similar to meprin beta-deficient mice, germ-free mice have attached mucus as they did not shed the membrane-anchored meprin beta into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin beta to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin beta cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin beta in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding. |
