Structure and biosynthesis of human salivary mucins.

• Authors: Anna Zalewska , Krzysztof Zwierz , Krzysztof Żółkowski , Andrzej Gindzieński
• Languages of publication: EN

Abstracts

EN

Human salivary glands secrete two types of mucins: oligomeric mucin (MG1) with molecular mass above 1 MDa and monomeric mucin (MG2) with molecular mass of 200-250 kDa. Monomers of MG1 and MG2 contain havily O-glycosylated tandem repeats located at the central domain of the molecules. MG1 monomers are linked by disulfide bonds located at sparsely glycosylated N- and C-end. MG1 are synthesized by mucous cells and MG2 by the serous cells of human salivary glands.

Keywords

EN

glycoproteins; human; saliva; mucins

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2000
• Volume: 47
• Issue: 4
• Pages: 1067-1079

Dates

published

2000

received

2000-03-9

revised

2000-09-1

accepted

2000-12-4

Contributors

author

Anna Zalewska

• Department of Pharmaceutical Biochemistry Institute of Chemistry, Medical Academy, Białystok, Poland

author

Krzysztof Zwierz

• Department of Pharmaceutical Biochemistry Institute of Chemistry, Medical Academy, Białystok, Poland

author

Krzysztof Żółkowski

• Department of Maxillofacial Surgery, Medical Academy, Białystok, Poland

author

Andrzej Gindzieński

• Department of General Chemistry, Medical Academy, Białystok, Poland

References

• 1. Nieuw Amerongen, A.V., Bolscher, J.G.M. & Veerman, E.C.I. (1995) Salivary mucins: Protective functions in relation to their diversity. Glycobiology 5, 733-740.
• 2. Mandel, I.D. (1987) The functions of saliva. J. Dent. Res. (Spec. Iss). 66, 623-627.
• 3. Gindzieński, A. & Zwierz, K. (1987) Isolation and fractionation of human gastric mucus gel. Biomed. Biochim. Acta 46, 165-176.
• 4. Paszkiewicz-Gadek, A., Gindzieński, A. & Porowska, H. (1995) The use of preparative polyacrylamide gel electrophoresis and electroelution for purification of mucus glycoproteins. Anal. Biochem. 226, 263-267.
• 5. Van Klinken, B.J.-W., Dekker, J., Büller, H.A. & Einerhand, A.W.C. (1995) Mucin gene structure and expression: Protection vs. adhesion. Am. J. Physiol. (Gastroint. Liver Physiol. 32) 269, G613-G-627.
• 6. Minkiewicz-Radziejewska, I., Gindzieński, A. & Zwierz, K. (2000) Disulfide-bound fragments of gastric mucin are 100- and 140-kDa proteins. Biochem. Biophys. Res. Commun. 270, 722-727.
• 7. Wu, A.M., Csako, G. & Herp, A. (1994) Structure, biosynthesis, and function of salivary mucins. Mol. Cell. Biochem. 137, 39-55.
• 8. Thornton, D.J., Khan, N., Mehrotra, R., Howard, M., Veerman, E., Packer, N.H. & Sheehan, J.K. (1999) Salivary mucin MG1 is comprised almost entirely of different glycosylated forms of MUC5B gene product. Glycobiology 9, 293-302.
• 9. Nielsen, P.A., Mandel, U., Therkildsen, M.H. & Clausen, H. (1996) Differential expression of human high-molecular-weight salivary mucin (MG1) and low-molecular-weight salivary mucin (MG2). J. Dent. Res. 75, 1820-1826.
• 10. Troxler, R.F., Iontcheva, I., Oppenheim, F.G., Nunes, D.P. & Offner, G.D. (1997) Molecular characterization of a major molecular weight mucin from human sublingual gland. Glycobiology 7, 965-973.
• 11. Milne, R.W. & Dawes, C. (1973) The relative contributions of different salivary glands to the blood group activity of whole saliva in humans. Vox Sang. 25, 298-307.
• 12. Edgerton, M. & Levine, M.J. (1992) Characterization of acquired denture pellicle from healthy and stomatitis patients. J. Prosthet. Dent. 68, 683-691.
• 13. Desseyn, J.-L., Guyonnet-Duperat, V., Porchet, N., Aubert, J.-P. & Laine, A. (1997) Human mucin gene MUC5B, the 10.7 kb large central exon encodes various alternate subdomains resulting in a super-repeat. Structural evidence for a 11p.15.5 gene family. J. Biol. Chem. 272, 3168-3178.
• 14. Van den Steen, Rudd, P.M., Dwek, R. & Opdenakker, G. (1998) Concepts and principles of O-linked glycosylation. Crit. Rev. Biochem. Mol. Biol. 33, 151-208.
• 15. Wickström, C., Davies, J.R., Eriksen, G.V., Veermans, E.C. & Carlsted, I. (1998) MUC5B is a major gel-forming, oligomeric mucin from human salivary gland, respiratory tract and endocervix: Identification of glycoforms and C-terminal cleavage. Biochem. J. 334, 685- 693.
• 16. Loomis, R.E., Prakobphol, A., Levine, M.J., Reddy, M.S. & Jones, P.C. (1987) Biochemical and biophysical comparison of two mucins from human submandibular-sublingual saliva. Arch. Biochem. Biophys. 258, 452-464.
• 17. Desseyn, J.-L., Aubert, J.-P., VanSeuningen, I., Porchet, N. & Laine, A. (1997) Genomic organization of the 3' region of the human mucin gene MUC5B. J. Biol. Chem. 272, 16873-16883.
• 18. Klein, A., Carnoy, Ch., Wieruszewski, J.-M., Strecker, G., Strang, A.-M., van Halbeck, H., Roussel, Ph. & Lamblin, G. (1992) The broad diversity of neutral and sialylated oligosaccharides derived from human salivary mucin. Biochemistry 31, 6152-6165.
• 19. Mancuso, D.J., Tuley, E.A., Westfield, L.A., Worral, N.K., Shelton-Inloes, B., Sorace, J.M., Alevy, Y.G. & Sadler, J.E. (1989) Structure of the gene for human von Willebrand factor. J. Biol Chem. 264, 19514-19527.
• 20. Hardy, D.M. & Garbers, D.L. (1995) A sperm membrane protein that binds in a species-specific manner to the egg extracellular matrix is homologous to von Willebrand factor. J. Biol. Chem. 270, 26025-26028.
• 21. Sheehan, J.K., Boot-Handford, R.P., Chantler, E., Carlstedt, I. & Thornton, D.J. (1991) Evidence for shared epitopes within the naked domains of human mucus glycoproteins. A study performed using polyclonal antibodies and electron microscopy. Biochem. J. 274, 293-296.
• 22. Antonyraj, K.J., Karunakaran, T. & Raj, P.A. (1998) Bactericidal activity and poly-L-proline II conformation of the tandem repeat sequence of human salivary glycoprotein (MG2). Arch. Biochem. Biophys. 356, 197-206.
• 23. Bobek, L.A., Tsai, H., Biesbrock, A.R. & Levine, M.J. (1993) Molecular cloning, sequence, and specificity of expression of the gene encoding the low molecular weight human salivary mucin (MUC 7). J. Biol. Chem. 268, 20563-20569.
• 24. Mehrotra, R., Thornton, D.J. & Sheehan, J.K. (1998) Isolation and physical characterization of MUC 7 (MG2) mucin from saliva: Evidence for self association. Biochem. J. 334, 415- 422.
• 25. Prakobphol, A., Thomsson, K.A., Hansson, G., Rosen, S.D., Singer, M.S., Phillips, N.J., Meddihradszky, K.F., Burlingame, A.L., Leffler, H. & Fisher, S. (1998) Human low-molecular- weight salivary mucin expresses the sialyl Lewisx determinant and has L-selectin ligand activity. Biochemistry 37, 4916-4927.
• 26. Levine, M.J., Reddy, M.S., Tabak, L.A., Loomis, R.E., Bergey, E.J., Jones, P.C., Cohen, R.E., Stinson, M.W. & Al-Hashimi, I. (1987) Structural aspects of saliva glycoproteins. J. Dent. Res. 66, 436-441.
• 27. Slomiany, B.L., Murthy, V.L.N. & Slomiany, A. (1993) Structural features of carbohydrate chains in human salivary mucins. Int. J. Biochem. 25, 259-265.
• 28. Slomiany, B.L., Piotrowski, J., Czajkowski, A. & Slomiany, A. (1993) Control of mucin molecular forms expression by salivary protease: Difference with caries. Int. J. Biochem. 25, 681-687.
• 29. Prakobphol, A., Tangemann, K., Rosen, S.D., Hoover, Ch.I., Leffler, H. & Fisher, S.J. (1999) Separate oligosaccharide determinants mediate interactions of the low-molecular-weight salivary mucins with neutrophils and bacteria. Biochemistry 38, 6817-6825.
• 30. Li, F., Wilkins, P.P., Crawley, S., Weinstein, J., Cummings, R.D. & McEver, R.P. (1996) Post-translational modifications of recombinant P-selectin glycoprotein ligand-1 required for binding to P- and E-selectin. J. Biol. Chem. 271, 3255-3264.
• 31. Nehrke, K. & Tabak, L.A. (1997) Biosynthesis of a low-molecular-mass rat submandibular gland mucin glycoprotein in COS 7 cells. Biochem. J. 323, 497-502.
• 32. McCool, D.J., Okada, Y., Forstner, J.F. & Forstner, G.G. (1999) Roles of calreticulin and calnexin during mucin synthesis in LS180 and HT29/A1 human colonic adenocarcinoma cells. Biochem. J. 341, 593-600.
• 33. Kapitonov, D. & Yu, R.K. (1999) Conserved domains of glycosyltransferases. Glycobiology 9, 961-978.
• 34. Porowska, H., Paszkiewicz-Gadek, A. & Gindzieński, A. (1999) Activity of partially purified UDP-N-acetyl-α-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase with different peptide acceptors. Acta Biochim. Polon. 46, 365-360.
• 35. Bennet, E.P., Hassan, H., Mandel, U., Hollingsworth, M.A., Akisawa, N., Ikematsu, Y., Merkx, G., vanKellel, A.G., Olofsson, S. & Clausen, H. (1999) Cloning and characterization of a close homologue of human UDP-N- acetyl-β-D-galactosamine: Polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. J. Biol. Chem. 274, 25362-25370.
• 36. Hagen, K.G.T., Hagen, F.K., Balys, M.M., Beres, T.M., van Wuyckhuyse, B. & Tabak, L.A. (1998) Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family. J. Biol. Chem. 273, 27749-27754.
• 37. Clausen, H. & Bennet, E.P. (1996) A family of UDP-GalNAc:polypeptide N-acetylgalactosaminyl-transferases control the initiation of mucin-type O-linked glycosylation. Glycobiology 6, 635-646.
• 38. Paulson, J.C. & Colley, K.J. (1989) Glycosyltransferases. Structure, localization, and control of cell type-specific glycosylation. J. Biol. Chem. 264, 17615-17618.
• 39. Rottger, S., White, R., Wandall, H.H., Bennet, E.A., Stark, A., Olivio, J., Whitehouse, C., Berger, E.G., Clausen, H. & Nilson, T. (1998) Differential localization of three human GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation occurs through the Golgi apparatus. J. Cell. Sci. 111, 45-60.
• 40. Bennet, E.P., Weghuis, D.D., Merkx, G., van Kessel, A.G., Eiberg, H. & Clausen, H. (1998) Genomic organization and chromosomal localization of three members of the UDP-N-acetyl- galactosamine:polypeptide N-acetylgalactosamine transferase family. Glycobiology 8, 547-555.
• 41. Wandall, H.H., Hassan, H., Mirgorodskaya, E., Kristensen, A.K., Roepstorff, P., Bennet, E.P., Nielsen, P.A., Hollingsworth, M.A., Burchell, J., Taylor-Papadamitriou, J. & Clausen, H. (1997) Substrate specificities of three members of the human UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminetransferase family. J. Biol. Chem. 272, 23503-23514.
• 42. Mandel, U., Hassan, H., Therkildsen, M.H., Rygaard, J., Jakobsen, M.H., Juhl, B.R., Dabelsteen, E. & Clausen, H. (1999) Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: Immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family. Glycobiology 9, 43-52.
• 43. Field, M.C. & Wainwright, L.J. (1995) Molecular cloning of eucaryotic glycoprotein and glycolipid glycosyltransferases: A survey. Glycobiology 5, 463-472.
• 44. Beum, P.V., Singh, J., Burdick, M., Hollongsworth, M.A. & Cheng, P.W. (1999) Expression of core 2 β1,6-N-acetyl-glucosaminyltransferase in a human pancreatic cancer cell line results in altered expression of MUC1 tumor-associated epitopes. J. Biol. Chem. 274, 24641-24648.
• 45. Barran, P., Fellinger, W., Warren, Che, E., Dennis, J.W. & Ziltener, H.J. (1997) Modification of CD 43 and other lymphocyte O-glycoproteins by core 2 N-acetylglucosaminyl transferase. Glycobiology 7, 129-136.
• 46. Granovsky, M., Fode, C., Warren, C.E., Campbell, R.M., Marth, J.D., Pierce, M., Fregien, N. & Dennis, J.W. (1995) GlcNAc-transferase V and core GlcNAc-transferase expression in the developing mouse embryo. Glycobiology 5, 797-806.
• 47. Li, F., Wilkins, P.P., Crawley, S., Weinstein, J., Cummings, R.D. & McEver, R.P. (1996) Post-translational modifications of recombinant P-selectin glycoprotein ligand-1 required for binding to P- and E-selectins. J. Biol. Chem. 271, 3255-3264.
• 48. Kapadia, A., Feizi, T. & Evans, M.J. (1981) Changes in the expression and polarization of blood group I and i antigens in post-implantation embryos and teratocarcinomas of mouse associated with cell differentiation. Exp. Cell Res. 131, 185-195.
• 49. Schachter, H. & Brockhausen, I. (1989) The biosynthesis of branched O-glycans. Symp. Soc. Exp. Biol. 43, 1-26.
• 50. Gooi, H.C., Feizi, T., Kapadia, A., Knowles, B.B., Solter, D. & Evans, M.J. (1981) Stage- specific embryonic antigen involves α1-3 fucosylated type 2 blood group chains. Nature 292, 156-158.
• 51. Lloyd, K.O., Kabat, E.A. & Licerio, E. (1968) Immunochemical studied on blood groups XXXVIII. Structures and activities of oligosaccharides produced by alkaline degradation of blood-group Lewisa substance. Proposed structure of the carbohydrate chains of human blood-group A, B, H, Lea, and Leb substance. Biochemistry 7, 2976-2990.
• 52. Abe, K., McKibbin, J.M. & Hakomori, S.I. (1983) The monoclonal antibody directed to difucosylated type 2 chain (Fucα1-2 Galβ1-4[Fucα1-3] GlcNAc), Y determinant. J. Biol. Chem. 258, 11793-11797.