Figure 2

MUC2 in colonic mucosa. A Synthesis, secretion and organization of colonic mucosa. The first stage in the biosynthesis of MUC2 is the formation of MUC2 monomer as an N-glycosylated apoprotein in the endoplasmic reticulum. Subsequently, MUC2 dimers are formed when intermolecular disulfide bonds bridge between the C-terminal cysteine knot domains. During transit through the Golgi apparatus, MUC2 dimers become heavily O-glycosylated. Complete glycosylation of the dimers occurs in Golgi where trimerization through disulfide bonds at the N-terminus forms protease-resistant trimers. The fully glycosylated and processed MUC2 is densely packed and stored in secretory granules/vesicles and released through constitutive or stimulated secretory mechanisms. Once released, MUC2 is organized into the firmly adherent inner layer. At a certain distance from the epithelium, this layer is converted into the loose outer layer through proteolytic cleavage and expansion. Mucus also contains immunoglobulins and other proteins. B MUC2 structure. The protein core consists of five different regions. Segment (a) and (b) are two central repetitive regions rich in potential O-glycosylation sites, to which branched carbohydrate chains of 4–12 sugars are O-glycosidically linked to form a closely packed sheath around the central protein core. Segment (a), also known as VNTR domain, is a large domain that contains 50–100 “variable number of tandem repeats (VNTRs)” of 23 amino acids, in particular, threonine. Segment (b), also called PTS domain, is a 347 amino acid domain, containing irregular repeats rich in proline, threonine and serine (PTS). These two segments are linked together by segment (c) which is a 148 amino acid, cysteine containing region. Segments (d) and (e) are extensive peptide chains rich in cysteine located at the C and N terminal ends, respectively, containing D domains with sequence homology to von Willebrand factor. These regions are the presumed sites for end to end polymerization of mucin subunits.