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Biological functions of proteoglycans: use of specific inhibitors of proteoglycan synthesis

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Abstract

The use of specific inhibitors of proteoglycan synthesis have demonstrated essential functions for these molecules. Proteoglycans do not appear to be essential for cell viability or proliferation but are necessary for stable assembly of ECM and functional cell-ECM interaction. Because of their ability to nearly completely abolish ECM assembly in cell culture systems, proteoglycan synthesis inhibitors are useful tools to examine effects of ECM on the phenotypic behavior of cells.

Despite its usefulness, the use of proteoglycan synthesis inhibitors has some drawbacks. The most significant of these is the fact that synthesis of all proteoglycans is inhibited, making it difficult to assign a particular function to a specific proteoglycan type. For this reason, inhibition studies need to be done in conjunction with additional biochemical, immunological or molecular biological studies.

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References

  1. Hascall VC, Hascall GK: Proteoglycans. In: ED Hay (ed.) Cell Biology of Extracellular Matrix. Plenum Press, New York, 1981, pp 39–63

    Google Scholar 

  2. Hook M, Kjellen L, Johansson S, Robinson J: Cell surface glycosaminoglycans. Ann Rev Biochem 53: 847–869, 1984

    Google Scholar 

  3. Ruoslahti E: Proteoglycans in cell regulation. J Biol Chem 264: 13369–13372, 1989

    Google Scholar 

  4. Nuwayhid N, Glaser JH, Johnson JC, Conrad HE, Hauser SC, Hirschberg CB: Xylosylation and glucuronosylation reactions in rat liver golgi apparatus and endoplasmic reticulum. J Biol Chem 261: 12936–12941, 1986

    Google Scholar 

  5. Schwartz NB, Galligani L, Ho P-L, Dorfman A: Stimulation of synthesis of free chondroitin sulfate chains by β-D-xylosides in cultured cells. Proc Natl Acad Sci USA 71: 4047–4051, 1974

    Google Scholar 

  6. Carey DJ, Rafferty CM, Todd MS: Effects of inhibition of proteoglycan synthesis on the differentiation of cultured rat Schwann cells. J Cell Biol 105: 1013–1021, 1987

    Google Scholar 

  7. Hamati HF, Britton EL, Carey DJ: Inhibition of proteoglycan synthesis alters extracellular matrix deposition, proliferation, and cytoskeletal organization of rat aortic smooth muscle cells in culture. J Cell Biol 108: 2495–2505, 1989

    Google Scholar 

  8. Thompson HA, Spooner BS: Inhibition of branching morphogenesis and alteration of glycosaminoglycan biosynthesis in salivary glands treated with β-D-xyloside. Dev Biol 89: 417–424, 1982

    Google Scholar 

  9. Bunge RP, Bunge MB, Eldridge CF: Linkage between axonal ensheathment and basal lamina production by Schwann cells. Ann Rev Neurosci 9: 305–328, 1986

    Google Scholar 

  10. Cornbrooks CJ, Carey DJ, McDonald JA, Timpl R, Bunge RP: In vivo and in vitro observations on laminin production by Schwann cells. Proc Natl Acad Sci USA 80: 3850–3854, 1983

    Google Scholar 

  11. Carey DJ, Eldridge CF, Cornbrooks CJ, Timpl R, Bunge RP: Biosynthesis of type IV collagen by cultured rat Schwann cells. J Cell Biol 97: 473–479, 1983

    Google Scholar 

  12. Mehta H, Orphe C, Todd MS, Cornbrooks CJ, Carey DJ: Synthesis by Schwann cells of basal lamina and membrane associated heparan sulfate proteoglycans. J Cell Biol 101: 660–666, 1985

    Google Scholar 

  13. Carey DJ, Evans DM: Membrane anchoring of heparan sulfate proteoglycans by phosphatidylinositol and kinetics of synthesis of peripheral and detergent-solubilized proteoglycans in Schwann cells. J Cell Biol 108: 1891–1897, 1989

    Google Scholar 

  14. Carey DJ, Stahl RC: Identification of a lipid-anchored heparan sulfate proteoglycan in Schwann cells. J Cell Biol in press, 1990

  15. Wight TN: Cell biology of arterial proteoglycans. Arteriosclerosis 9: 1–20, 1989

    Google Scholar 

  16. Schwartz SM, Campbell GR, Campbell JH: Replication of smooth muscle cells in vascular disease. Circulation Research 58: 427–444, 1986

    Google Scholar 

  17. Carey DJ: Control of growth and differentiation of vascular cells by extracellular matrix proteins. Ann Rev Physiol in press, 1991

  18. Trelstad RL, Silver FH: Matrix Assembly. In: ED Hay (ed.) Cell Biology of Extracellular Matrix. Plenum Press, New York, 1981, pp 179–215

    Google Scholar 

  19. Yurchenko PD, Schittny JC: Molecular architecture of basement membranes. FASEB 14: 1577–1590, 1990

    Google Scholar 

  20. Timpl R: Structure and biological activity of basement membrane proteins. Eur J Biochem 180: 487–502, 1989

    Google Scholar 

  21. Heremans A, DeCock B, Cassiman JJ, Van den Berghe H, David G: The core protein of the matrix-associated heparan sulfate proteoglycan binds to fibronectin. J Biol Chem 265: 8716–8724, 1990

    Google Scholar 

  22. Carey DJ, Crumbling DM, Stahl RC, Evans DM: Association of cell surface heparan sulfate proteoglycans of Schwann cells with extracellular matrix proteins. J Biol Chem in press, 1990

  23. Ruoslahti E: Fibronectin and its receptors. Ann Rev Biochem 57: 375–413, 1988

    Google Scholar 

  24. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K: Interaction of plasma membrane fibronectin receptor with talin-a transmembrane linkage. Nature 320: 531–533, 1986

    Google Scholar 

  25. Otey CA, Pavalko FM, Burridge K: An interaction between α-actinin and the β1 integrin subunit in vitro. J Cell Biol 111: 721–729, 1990

    Google Scholar 

  26. Saunders S, Jalkanen M, O'Farrell S, Bernfield M: Molecular cloning of syndecan, an integral membrane proteoglycan. J Cell Biol 108: 1547–1556, 1989

    Google Scholar 

  27. Marynen P, Zhang J, Cassiman J-J, Van den Berghe H, David G: Partial primary structure of 48- and 90-kilodalton core proteins of the cell surface-associated heparan sulfate proteoglycans of lung fibroblasts. J Biol Chem 264: 7017–7024, 1989

    Google Scholar 

  28. Koda JE, Rapraeger A, Bernfield M: Heparan sulfate proteoglycans from mouse mammary epithelial cells: cell surface proteoglycan as a receptor for interstitial collagens. J Biol Chem 260: 8157–8162, 1985

    Google Scholar 

  29. Saunders S, Bernfield M: Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix. J Cell Biol 106: 423–430, 1988

    Google Scholar 

  30. Sun X, Mosher DF, Rapraeger A: Heparan sulfate-mediated binding of epithelial cell surface proteoglycan to thrombospondin. J Biol Chem 264: 2885–2889, 1989

    Google Scholar 

  31. Mali M, Jaakkola P, Arvilommi A-M, Jalkanen M: Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans. J Biol Chem 265: 6884–6889, 1990

    Google Scholar 

  32. Carey D, Todd M: A cytoskeleton-associated plasma membrane heparan sulfate proteoglycan in Schwann cells. J Biol Chem 261: 7518–7525, 1986

    Google Scholar 

  33. Carey DJ, Rafferty CM, Schramm MS: Association of heparan sulfate proteoglycan and laminin with the cytoskeleton in rat liver. J Biol Chem 262: 3376–3381, 1987

    Google Scholar 

  34. Woods A, Couchman JR, Hook M: Heparan sulfate proteoglycans of rat embryo fibroblasts: a hydrophobic form may link cytoskeleton and matrix components. J Biol Chem 260: 10872–10879, 1985

    Google Scholar 

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Carey, D.J. Biological functions of proteoglycans: use of specific inhibitors of proteoglycan synthesis. Mol Cell Biochem 104, 21–28 (1991). https://doi.org/10.1007/BF00229799

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