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GPI-GlcNAc Transferase: Complex of PIG-A, PIG-C, PIG-H, hGPI1, and PIG-P

  • Norimitsu Inoue
  • Taroh Kinoshita

Abstract

Glycosylphosphatidylinositols (GPIs) anchor proteins to the cellular plasma membrane in a wide range of eukaryotic organisms from yeasts to mammals (Kinoshita et al. 1997). The GPI-anchor is transferred en bloc to the carboxyl-terminus of protein precursors in the endoplasmic reticulum (ER). Attachment of the GPI-anchor to the proteins is essential for their expression on the cell surface. Synthesis of the GPI- anchor is initiated by transferring GlcNAc to phosphatidylinositol (PI) and proceeds by de-N-acetylation of GlcNAc, acylation of myoinositol, and addition of three man- noses and three ethanolamine phosphates in mammalian cells (see Appendix Map- 5). The basic structure and biosynthetic pathway are conserved in various organisms. The UDP-GlcNAc:PI-α1-4GlcNAc transferase (GPI-GlcNAc transferase, or GPI-GnT) catalyzes the first reaction in the biosynthesis of the GPI-anchor.

Keywords

Paroxysmal Nocturnal Hemoglobinuria Fatty Acyl Chain Conditional Knockout Mouse Piga Gene Paroxysmal Nocturnal Hemoglobinuria Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ferguson MA (1999) The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research. J Cell Sci 112:2799–2809PubMedGoogle Scholar
  2. Hong Y, Ohishi K, Watanabe R, Endo Y, Maeda Y, Kinoshita T (1999) GPI1 stabilizes an enzyme essential in the first step of glycosylphosphatidylinositol biosynthesis. J Biol Chem 274:18582–18588PubMedCrossRefGoogle Scholar
  3. Inoue N, Watanabe R, Takeda J, Kinoshita T (1996) PIG-C, one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2. Biochem Biophys Res Commun 226:193–199PubMedCrossRefGoogle Scholar
  4. Kamitani T, Chang HM, Rollins C, Waneck GL, Yeh ETH (1993) Correction of the class H defect in glycosylphosphatidylinositol anchor biosynthesis in Ltk-cells by a human cDNA clone. J Biol Chem 268:20733–20736PubMedGoogle Scholar
  5. Kinoshita T, Ohishi K, Takeda J (1997) GPI-anchor synthesis in mammalian cells: genes, their products, and a deficiency. J Biochem 122:251–257PubMedCrossRefGoogle Scholar
  6. Leidich SD, Orlean P (1996) Gpil, a Saccharomyces cerevisiae protein that participates in the first step in glycosylphosphatidylinositol anchor synthesis. J Biol Chem 271:27829–27837PubMedCrossRefGoogle Scholar
  7. Leidich SD, Drapp DA, Orlean P (1994) A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis. J Biol Chem 269:10193–10196PubMedGoogle Scholar
  8. Leidich SD, Kostova Z, Latek RR, Costello LC, Drapp DA, Gray W, Fassler JS, Orlean P (1995) Temperature-sensitive yeast GPI anchoring mutants gpi2 and gpi3 are defective in the synthesis of N-acetylglucosaminyl phosphatidylinositol: cloning of the GPI2 gene. J Biol Chem 270:13029–13035PubMedCrossRefGoogle Scholar
  9. Lipke PN, Ovalle R (1998) Cell wall architecture in yeast: new structure and new challenges. J Bacteriol 180:3735–3740PubMedGoogle Scholar
  10. Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M, Maeda K, Kitani T, Kinoshita T (1993) Cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science 259:1318–1320PubMedCrossRefGoogle Scholar
  11. Murakami Y, Kinoshita T, Maeda Y, Nakano T, Kosaka H, Takeda J (1999) Different roles of glycosylphosphatidylinositol in various hematopoietic cells as revealed by model mice of paroxysmal nocturnal hemoglobinuria. Blood 94:2963–2970PubMedGoogle Scholar
  12. Nozaki M, Ohishi K, Yamada N, Kinoshita T, Nagy A, Takeda J (1999) Developmental abnormalities of glycosylphosphatidylinositol-anchor-deficient embryos revealed by Cre/loxP system. Lab Invest 79:293–299PubMedGoogle Scholar
  13. Schonbachler M, Horvath A, Fassler J, Riezman H (1995) The yeast sptl4 gene is homologous to the human PIG-A gene and is required for GPI anchor synthesis. EMBO J 14:1637–1645PubMedGoogle Scholar
  14. Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, Takahashi M, Kitani T, Kinoshita T (1993) Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell 73:703–711PubMedCrossRefGoogle Scholar
  15. Tarutani M, Itami S, Okabe M, Ikawa M, Tezuka T, Yoshikawa K, Kinoshita T, Takeda J (1997) Tissue specific knock-out of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development. Proc Natl Acad Sci USA 94:7400–7405PubMedCrossRefGoogle Scholar
  16. Tremml G, Dominguez C, Rosti V, Zhang Z, Pandolfi PP, Keller P, Bessler M (1999) Increased sensitivity to complement and a decreased red cell life span in mice mosaic for a nonfunctional Piga gene. Blood 94:2945–2962PubMedGoogle Scholar
  17. Ullman CG, Perkins SJ (1997) A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem J 326:929–942Google Scholar
  18. Vossen JH, Ram AF, Klis FM (1995) Identification of SPT14/CWH6 as the yeast homologue of hPIG-A, a gene involved in the biosynthesis of GPI anchors. Biochim Biophys Acta 1243:549–551PubMedCrossRefGoogle Scholar
  19. Watanabe R, Inoue N, Westfall B, Taron CH, Orlean P, Takeda J, Kinoshita T (1998) The first step of glycosylphosphatidylinositol biosynthesis is mediated by a complex of PIG-A, PIG-H, PIG-C and GPU. EMBO J 17:877–885PubMedCrossRefGoogle Scholar
  20. Watanabe R, Murakami Y, Marmor MD, Inoue N, Maeda Y, Hino J, Kangawa K, Julius M, Kinoshita T (2000) Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG-P and is regulated by DPM2. EMBO J 19:4402–4411PubMedCrossRefGoogle Scholar
  21. Watanabe R, Kinoshita T, Masaki R, Yamamoto A, Takeda J, Inoue N (1996) PIG-A and PIG-H, which participate in glycosylphosphatidylinositol anchor biosynthesis, form a protein complex in the endoplasmic reticulum. J Biol Chem 271:26868–26875PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2002

Authors and Affiliations

  • Norimitsu Inoue
    • 1
  • Taroh Kinoshita
    • 1
  1. 1.Department of ImmunoregulationResearch Institute for Microbial Diseases, Osaka UniversityOsakaJapan

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