Synthesis and macromolecular organization of gastrointestinal mucin

• Autorzy: Slomiany A , Slomiany B.L.
• Języki publikacji: EN

Abstrakty

EN

Mucus glycoproteins (mucins), the principal determinants of mucus protective qualities and mucosal defense, are studied extensively to define pathological aberrations in the relation to gastrointestinal disease and to develop the mucous barrier strengthening agents. Recent work from our laboratory provided evidence as to the initial stages of the gastrointestinal mucin synthesis, molecular size of the apomucin, its macromolecular organization and interaction with other elements of gastrointestinal mucus. Using monoclonal antibodies against apomucin (clone 1H7), O- glycosylated with N-acetylgalactosamine apomucin (clone 2B4), and that against carboxyl terminal of the apomucin (clone 3G12), the mucin synthesizing polysomes were isolated and glycosylated peptides ranging in size from 6-60kDa identified. The in vitro synthesis in the cell-free system also afforded 60-64kDa products recognized by 1H7 and 3G12 antimucin MAbs. The obtained results provided evidence that the mucin core consists of 60kDa peptide which at cotranslational stage is O-glycosylated with N-acetylgalactosamine. Studies on mucin polymer assembly revealed that mucin preparations prepared by equilibrium density gradient centrifugation and Sepharose 2B chromatography (Mantle, M., Mantle, D., and Allen, A. (1981) Biochem. J. 195, 277-285) are not completely purified and contain DNA and extraneous proteins. The evidence was obtained that so called mucin “link protein”, 118kDa glycopeptide, is a N-glycosylated fragment of fibronectin, whereas the supposedly native undegraded mucin isolated by Carlstedt et al. (Biochem. J. (1983) 211, 13-22) was found to contain mucin-fibronectin-DNA complexes. The general picture that emerged from the studies is that the pure mucin consists of 60kDa glycosylated peptides only. The carboxyl terminal (8-12kDa fragment) of these peptides is not glycosylated (naked) and is responsible for mucin interaction with fibronectin and other fibronectin-like extracellular matrix proteins. While the formation of the mucosal coat depends on many other factors and extracellular components, our findings on mucin structure and interaction with the extracellular matrix proteins provide explanation as to the possible mechanism of mucin adherence to the epithelial surfaces.

Słowa kluczowe

EN

gastrointestinal tract; mucin; monoclonal antibody; fibronectin; glycopeptide

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 1992
• Tom: 43
• Numer: 2
• Opis fizyczny: p.115-138,fig.

Twórcy

autor

Slomiany A

• Research Center University Heights, 110 Bergen Street, C813, Newark, NJ 07103-2400, USA

autor

Slomiany B.L.

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