Gel-forming mucins

Fig. 2.1 Multi-domain structural organization of gastrointestinal gel-forming mucins. Schematic drawings (not at scale) of the different domains found in gastrointestinal mucins and their roles. Note that while the cysteine-rich domains (D-, CS-, C-, and CK-domains) have a similar length among mucin alleles, the O-glycosylated regions, except in the case of MUC5B, differ in size, a feature not shown in the drawings...

Besides the prominent mucin domains, gel-forming mucins have other domains (i.e., CS-, D-, C-, and CK-domains as shown in Fig. 2.1) (Perez-Vilar and Hill 1999 Dekker et al. 2002) characterized by being (a) under-glycosylated, although most have one or more N-linked oligosaccharide chains (see Section... 

Three NH2-terminal D-domains, designated Dl, D2, and D3, are found in all gel-forming mucins whereas a fourth D-domain, named D4, is at the COOH terminus of MUC2, MUC5AC, and MUC5B but not MUC6 and MUC19 (Fig. 2.1) (Perez-Vilar and Hill 1999 Dekker et al. 2002 Chen et al. 2004 Rousseau et al. 2004). A partial D-domain, D , is between D2 and D3 in all of them. Each... 

Fig. 2.2 Different levels of structural organization in gel-forming mucins. From the biochemical point of view (a), mucin polypeptides have very complex multi-domain structures and glycosylation patterns and thousands of amino acids per monomer. Moreover, the monomers are assembled into disulfide-linked oligomers/multimers that have contour sizes of several microns.

Fig. 2.4 Biosynthesis of gel-forming mucins. Schematic representation of the major steps occurring during the biosynthesis of mucins. Mucin biosynthesis is a sequential process that starts in the endoplasmic reticulum and ends in the trans-compartments of the Golgi complex. Formation of disulfide-linked oligomers/multimers involves two steps dimerization in the endoplasmic reticulum and interdimeric disulfide bonding in the Golgi complex. O-Glycosy-lation of dimeric precursors results in more extended but still flexible chains. See text for further details. Rectangles indicate the NH-terminal D-domains while circles and the bars represent the COOH-terminal CK-domains and the O-glycan chains, respectively...

Once the mucin dimeric precursors reach the Golgi complex, they are O-glycosylated and N-glycosylation is completed. In vitro studies with purified, de-glycosylated gel-forming mucins (Rose et al. 1984, Shogren et al. 1989 ... 

Perez-Vilar J. and Mabolo R. (2007) Gel-forming Mucins. Notions from in vitro studies. Histol Histopathol. 22 455-464... 

MUC2, also known as intestinal-type secretory mucin, goblet-type mucin, or gel-forming mucin, is not constitutively expressed in the pancreas or ampullary ductules with the exception of the scattered goblet cells, where it functions as a protective barrier. It is a product... 

Figure 1 Model of a gel-forming mucin in the intestinai tract. A iarge secreted mucin is depicted, such as MUC2 in the coion. The VNTR (variabie number of tandem repeat) region is rich in Ser, Thr, and Pro and is highiy O-giycosyiated therefore, the peptide assumes an extended bottie brush -iike conformation. The majority of coionic mucin 0-giycans appear to have extended core 3 structures but extended core 1 and other O-giycan structures are also found. Both ends of the molecule have Cys-rich regions and other domains that may be involved in the polymerization to form large molecules of several million daltons.

The functions of the large gel-forming mucins include lubrication of the epithelial surfaces and protection from chemical and physical impact and microbial damage. Bacteria, viruses, and other microbes bind to mucin-type 0-glycans and are trapped by the viscous mucus layer. This may prevent their migration toward the epithelial cell surface and support their removal by ciliary action. Bacteria can also use the carbohydrate moieties of mucins as nutrients. 

We are investigatii the solution properties of mucin glycoproteins in order to understand the relationship between their chemical structure and viscoelastic properties. Gel-forming mucins such as tracheo-... 

Secreted gel-forming mucins MUC2 llplS.S Small intestine, colon, 23 540... 

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