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Glycosyl-phosphatidylinositol molecules of the parasite and the host

  • M. A. J. Ferguson (a1), J. S. Brimacombe (a2), S. Cottaz (a2), R. A. Field (a1) (a2), L. S. Güther (a1), S. W. Homans (a1), M. J. McConville (a1), A. Mehlert (a1), K. G. Milne (a1), J. E. Ralton (a1), Y. A. Roy (a1), P. Schneider (a1) and N. Zitzmann (a1)...


The glycosyl-phosphatidylinositol (GPI) protein-membrane anchors are ubiquitous among the eukaryotes. However, while mammalian cells typically express in the order of 100 thousand copies of GPI-anchor per cell, the parasitic protozoa, particularly the kinetoplastids, express up to 10–20 million copies of GPI-anchor and/or GPI-related glycolipids per cell. Thus GPI-family members dominate the cell surface molecular architecture of these organisms. In several cases, GPI-anchored proteins, such as the variant surface glycoprotein (VSG) of the African trypanosomes, or GPI-related glycolipids, such as the lipophosphoglycan (LPG) of the Leishmania, are known to be essential for parasite survival and infectivity. The highly elevated levels and specialised nature of GPI metabolism in the kinetoplastid parasites suggest that the GPI biosynthetic pathways might be good targets for the development of chemotherapeutic agents. This article introduces the range of GPI structures found in protozoan parasites, and their mammalian hosts, and discusses some aspects of GPI biosynthesis.



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Bahr, V., Stierhof, Y.-D., Ilg, T., Demar, M., Quinten, M. & Overath, P. (1993). Expression of lipophosphoglycan, high-molecular weight phosphoglycan and glycoprotein gp63 in promastigotes and amastigotes of Leishmania mexicana. Molecular and Biochemical Parasitology 58, 107–22.
Clayton, C. E. & Mowatt, M. R. (1989). The procyclic acidic repetitive proteins of Trypanosoma brucei: Purification and post-translational modification. Journal of Biological Chemistry 264, 15088–93.
Cottaz, S., Brimacombe, J. S. & Ferguson, M. A. J. (1993). Parasite glycoconjugates. Part 1. The synthesis of some early and related intermediates in the biosynthetic pathway of glycosyl–phosphatidylinositol membrane anchors. Journal Chem. Soc. Perkin Trans 1, 2945–51.
Cross, G. A. M. (1990). Cellular and genetic aspects of antigenic variation in trypanosomes. Annual Reviews of Immunology 8, 83100.
Doering, T. L., Pessin, M. S., Hoff, E. F., Hart, G. W., Raben, D. M. & Englund, P. T. (1993). Trypanosome metabolism of myristate, the fatty acid required for the variant surface glycoprotein membrane anchor. Journal of Biological Chemistry 268, 9215–22.
Doering, T. L., Raper, J., Buxbaum, L. U., Adams, S. P., Gordon, J. I., Hart, G. W. & Englund, P. T. (1991). An analog of myristic acid with selective toxicity for African trypanosomes. Science 252, 1851–4.
Englund, P. T. (1993). The structure and biosynthesis of glycosyl phosphatidylinositol protein anchors. Annual Reviews of Biochemistry 62, 121–38.
Ferguson, M. A. J. (1992). Glycosyl–phosphatidylinositol membrane anchors: The tale of a tail. Biochemical Society Transactions 20, 243–56.
Ferguson, M. A. J., Homans, S. W., Dwek, R. A. & Rademacher, T. W. (1988). Glycosyl–phosphatidylinositol moiety that anchors Trypanosoma brucei variant surface glycoprotein to the membrane. Science 239, 753–9.
Ferguson, M. A. J., Masterson, W. J., Homans, S. W. & McConville, M. J. (1991). Evolutionary aspects of GPI metabolism in kinetoplastid parasites. Cell Biological International Reports 15, 9911005.
Ferguson, M. A. J., Murray, P., Rutherford, H. & McConville, M. J. (1993). A simple purification of procyclic acidic repetitive protein and demonstration of a sialylated glycosyl–phosphatidylinositol membrane anchor. Biochemical Journal 291, 51–5.
Homans, S. W., Edge, C. J., Ferguson, M. A. J., Dwek, R. A. & Rademacher, T. W. (1989). Solution structure of the glycosylphosphatidylinositol membrane anchor glycan of Trypanosoma brucei variant surface glycoprotein. Biochemistry 28, 2881–7.
Homans, S. W. & Forster, M. (1992). Application of restrained minimization, simulated anealing and molecular dynamics simulations for the conformational analysis of oligosaccharides. Glycobiology 2, 143–51.
Homans, S. W., Mehlert, A. & Turco, S. J. (1992). Solution structure of the lipophosphoglycan of Leishmania donovani. Biochemistry 31, 654–61.
Ilg, T., Etges, R., Overath, P., McConville, M. J., Thomas-Oates, J., Thomas, J., Homans, S. W. & Ferguson, M. A. J. (1992). Structure of Leishmania mexicana lipophosphoglycan. Journal of Biological Chemistry 267, 6834–40.
Lisanti, M. P., Field, M. C., Caras, I. W. J., Menon, A. K. & Rodriguez-Boulan, E. (1991). Mannosamine, a novel inhibitor of glycosyl–phosphatidylinositol incorporation into proteins. EMBO Journal 10, 1969–77.
Masterson, W. J. & Ferguson, M. A. J. (1991). Phenylmethanesulphonyl fluoride inhibits GPI anchor biosynthesis in the African trypanosome. EMBO Journal 10, 2041–5.
McConville, M. J. & Blackwell, J. M. (1991). Developmental changes in the glycosylated phosphatidylinositols of Leishmania donovani: Characterization of the promastigote and amastigote glycolipids. Journal of Biological Chemistry 266, 15170–9.
McConville, M. J., Collidge, T. A. C., Ferguson, M. A. J. & Schneider, P. (1993). The glycoinositolphospholipids of Leishmania mexicana promastigotes: Evidence for the presence of three distinct pathways of glycolipid biosynthesis. Journal of Biological Chemistry 268, 15595–604.
McConville, M. J. & Ferguson, M. A. J. (1993). The structure, biosynthesis and function of glycoslyated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochemical Journal 294, 305–24.
McConville, M. J., Homans, S. W., Thomas-Oates, J. E., Dell, A. & Bacic, A. (1990 a). Structures of the glycoinositolphospholipids from Leishmania major. Journal of Biological Chemistry 265, 7385–94.
McConville, M. J., Thomas-Oates, J. E., Ferguson, M. A. J. & Homans, S. W. (1990 b). Structure of the lipophosphoglycan from Leishmania major. Journal of Biological Chemistry 265, 19611–23
McConville, M. J., Turco, S. J., Ferguson, M. A. J. & Sacks, D. L. (1992). Developmental modification of lipophosphoglycan during the differentiation of Leishmania major promastigotes to an infectious stage. EMBO Journal 11, 3593–600
Menon, A. K., Eppinger, M., Mayor, S. & Schwarz, R. T. (1993). Phosphatidylethanolamine is the donor of the terminal phosphoethanolamine group in trypanosome glycosylphosphatidylinositols. EMBO Journal 12, 1907–14.
Milne, K. G., Ferguson, M. A. J. & Masterson, W. J. (1992). Inhibition of the GlcNAc transferase of glycosylphosphatidylinositol anchor biosynthesis in African trypanosomes. European Journal of Biochemistry 208, 309–14.
Milne, K. G., Field, R. A. & Ferguson, M. A. J. (1993). Biosynthesis of glycosyl–phosphatidylinositol protein anchors in African trypanosomes. In New developments in lipid–protein interactions and receptor function (ed. Gustafson, J. A. & Wirtz, K. W. A.). NATO–ASI Series, Series A Vol. 246. Plenum Publishing Co., London pp. 275286.
Pan, Y.-T., Kamitani, T., Bhuvaneswaran, C., Hallaq, Y, Warren, C. D., Yeh, E. T. H. & Elbein, A. D. (1992). Inhibition of glycosylphosphatidylinositol anchor formation by mannosamine. Journal of Biological Chemistry 267, 21250–5.
Pimenta, P. F., Turco, S. J., McConville, M. J., Lawyer, P. G., Perkins, P. V. & Sacks, D. L. (1992). Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. Science 256, 1812–5.
Ralton, J. E., Milne, K. G., Güther, M. L. S., Field, R. A. & Ferguson, M. A. J. (1993). The mechanism of inhibition of glycosyl–phosphatidylinositol anchor biosynthesis in Trypanosoma brucei by mannosamine. Journal of Biological Chemistry 268, 24183–9.
Richardson, J. P., Beecroft, R. P., Tolson, D. L., Liu, M. K. & Pearson, T. W. (1988). Procyclin: an unusual immunodominant glycoprotein surface antigen from the procyclic stage of African trypanosomes. Molecular and Biochemical Parasitology 31, 203–16.
Roditi, I., Schwarz, H., Pearson, T. W., Beecroft, R. P., Liu, M. K., Richardson, J. P., Bühring, H-J., Bülow, R., Williams, R. O. & Overath, P. (1989). Procyclin gene expression and loss of the variant surface glycoprotein during differentiation of Trypanosoma brucei. Journal of Cellular Biology 108, 737–46.
Schneider, P., Rosal, J.-P., Ransijn, A., Ferguson, M. A. J. & McConville, M. J. (1993). Characterization of glycoinositol phospholipids in the amastigote stage of the protozoan parasite Leishmania major. Biochemical Journal 295, 555–64.
Thomas, J. R., McConville, M. J.Thomas-Oates, J. E., Homans, S. W., Ferguson, M. A. J., Gorin, P. A. J., Greis, K. D. & Turco, S. J., (1992). Refined structure of the lipophosphoglycan of Leishmania donovani. Journal of Biological Chemistry 267, 6829–33.


Glycosyl-phosphatidylinositol molecules of the parasite and the host

  • M. A. J. Ferguson (a1), J. S. Brimacombe (a2), S. Cottaz (a2), R. A. Field (a1) (a2), L. S. Güther (a1), S. W. Homans (a1), M. J. McConville (a1), A. Mehlert (a1), K. G. Milne (a1), J. E. Ralton (a1), Y. A. Roy (a1), P. Schneider (a1) and N. Zitzmann (a1)...


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