Glycosyl Phosphatidylinositol-Linked Glycoconjugates:Structure, Biosynthesis and function
The purpose of this review is to summarize the most recent advances on GPI research. tructural studies on GPI-linked glycoconjugates indicate that there are significant ariations in different organisms, although there is a conserved core structure. Furthermore, tructural studies suggest that in different cell types, there is an army oflycosyltransferases dedicated to the synthesis of GPI-linked glycoconjugates. Bio-hemical studies on the synthesis of these GPI-linked glycoconjugates suggest that not only many different enzymes are involved but also that enzymes from different cell types, nvolving in the conserved core structure can have different substrate specificity. Genetic loning of the yeast genes involved in synthesizing the core structure suggests that many of hese enzymes also have human homologues. However, paroxysmal nocturnal emogobinuria (PNH) is the only known human disease associated with the synthesis of GPI-linked glycoconjugates. Functional studies suggest that GPI-anchor can act as a signal or protein sorting and localization. Furthermore, GPI-linked receptors play an important ole in T-cell activation.
KeywordsParoxysmal Nocturnal Hemoglobinuria Trypanosoma Brucei Yeast Homologue Variant Surface Glycoprotein African Trypanosome
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- 7.Morita, Y., Acosta-Serrano, A., and Englund, P. T. (in press) The biosynthesis of GPI anchors, (Ernst, B., Sina, P. and Hart, G. eds), Weinheim, Wiley-VCH.Google Scholar
- 8.Kapteyn, J. C., Montijn, R. C., Vink, E., de la Cruz, J., Llobell, A., Douwes, J. E., Shimoi, H., Lipke, P. N., and Klis, F. M. (1996) Retention of Saccharomyces cerevisiae cell wall proteins through a phosphodiester-linked beta-1,3-/beta-1,6-glucan heteropolymer. Glycobiology., 6: 337–45.Google Scholar
- 11.Ralton, J. E. and McConville, M. J. (1998) Delineation of three pathways of glycosylphosphatidylinositol biosynthesis in Leishmania mexicana. Precursors from different pathways are assembled on distinct pools of phosphatidylinositol and undergo fatty acid remodeling. J Biol Chem., 273: 4245–57.CrossRefPubMedGoogle Scholar
- 13.Hilley, J. D., Zawadzki, J. L., McConville, M. J., Coombs, G. H., and Mottram, J. C. (2000) Leishmania mexicana Mutants Lacking Glycosylphosphatidylinositol (GPI):Protein Transamidase Provide Insights into the Biosynthesis and Functions of GPI-anchored Proteins. Mol Biol Cell., 11: 1183–1195.PubMedGoogle Scholar
- 18.Lipardi, C., Nitsch, L., and Zurzolo, C. (2000) Detergent-insoluble GPI-anchored proteins are apically sorted in fischer rat thyroid cells, but interference with cholesterol or sphingolipids differentially affects detergent insolubility and apical sorting. Mol Biol Cell., 11: 531–42.PubMedGoogle Scholar
- 19.Nosjean, O., Briolay, A. Roux, B. (1997) Mammalian GPI proteins: sorting, membrane residence and functions. Biochim Biophys Acta., 1331: 153–86.Google Scholar
- 22.Alfalah, M., Jacob, R., Preuss, U., Zimmer, K. P., Naim, H., and Naim, H. Y. (1999) 0-linked glycans mediate apical sorting of human intestinal sucrase-isomaltase through association with lipid rafts. Curr Biol., 9: 59–36.Google Scholar
- 28.Smith, T. K., Cottaz, S., Brimacombe, J. S., and Ferguson, M. A. (1996) Substrate specificity of the dolichol phosphate mannose: glucosaminyl phosphatidylinositol alphal-4- mannosyltransferase of the glycosylphosphatidylinositol biosynthetic pathway of African trypanosomes. J Biol Chem., 271: 6476–82.CrossRefPubMedGoogle Scholar
- 29.Sharma, D. K., Smith, T. K., Crossman, A., Brimacombe, J. S., and Ferguson, M. A. (1997) Substrate specificity of the N-acetylglucosaminyl-phosphatidylinositol de-N-acetylase of glycosylphosphatidylinositol membrane anchor biosynthesis in African trypanosomes and human cells. Biochem J., 328: 171–7.PubMedGoogle Scholar
- 31.Smith, T. K., Sharma, D. K., Crossman, A., Brimacombe, J. S., and Ferguson, M. A. (1999) Selective inhibitors of the glycosylphosphatidylinositol biosynthetic pathway of Trypanosoma brucei. ENBO J., 18: 5922–30.Google Scholar
- 32.Ferguson, M. A., Brimacombe, J. S., Brown, J. R., Crossman, A., Dix, A., Field, R. A., Guther, M. L., Milne, K. G., Sharma, D. K., and Smith, T. K. (1999) The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness. Biochim Biophys Acta., 1455: 327–40.CrossRefPubMedGoogle Scholar