1887

Abstract

Glycosylphosphatidylinositols (GPIs) are essential for viability in yeast and have key roles in cell wall construction. Assembly of GPIs includes the addition of a fourth, side-branching mannose (Man) to the third Man of the core GPI glycan by the Smp3 mannosyltransferase. The gene from the human pathogenic fungus has been cloned. complements the inviable null mutant and, when expressed in an / double mutant, it permits conversion of the Man-GPI precursor that accumulates in that mutant to a Man-GPI. One allele of was disrupted using the ura-blaster procedure, then the remaining allele was placed under the control of the glucose-repressible promoter. Repression of expression leads to accumulation of a GPI precursor glycolipid whose glycan headgroup contains three mannoses and bears a phosphodiester-linked substituent on its first Man. Under repressing conditions, cells exhibited morphological and cell wall defects and became inviable. CaSmp3p therefore adds a fourth, 1,2-linked Man to trimannosyl GPI precursors in and is necessary for viability. Because addition of a fourth Man to GPIs is of less relative importance in mammals, Smp3p is a potential antifungal target.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.27254-0
2004-10-01
2019-11-14
Loading full text...

Full text loading...

/deliver/fulltext/micro/150/10/mic1503115.html?itemId=/content/journal/micro/10.1099/mic.0.27254-0&mimeType=html&fmt=ahah

References

  1. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. ( 1990; ). Basic local alignment search tool. J Mol Biol 215, 403–410.[CrossRef]
    [Google Scholar]
  2. Backen, A. C., Broadbent, I. D., Fetherston, R. W., Rosamond, J. D., Schnell, N. F. & Stark, M. J. ( 2000; ). Evaluation of the CaMAL2 promoter for regulated expression of genes in Candida albicans. Yeast 16, 1121–1129.[CrossRef]
    [Google Scholar]
  3. Benachour, A., Sipos, G., Flury, I., Reggiori, F., Canivenc-Gansel, E., Vionnet, C., Conzelmann, A. & Benghezal, M. ( 1999; ). Deletion of GPI7, a yeast gene required for addition of a side chain to the glycosylphosphatidylinositol (GPI) core structure, affects GPI protein transport, remodeling, and cell wall integrity. J Biol Chem 274, 15251–15261.[CrossRef]
    [Google Scholar]
  4. Benghezal, M., Lipke, P. N. & Conzelmann, A. ( 1995; ). Identification of six complementation classes involved in the biosynthesis of glycosylphosphatidylinositol anchors in Saccharomyces cerevisiae. J Cell Biol 130, 1333–1344.[CrossRef]
    [Google Scholar]
  5. Canivenc-Gansel, E., Imhof, I., Reggiori, F., Burda, P., Conzelmann, A. & Benachour, A. ( 1998; ). GPI anchor biosynthesis in yeast: phosphoethanolamine is attached to the α1,4-linked mannose of the complete precursor glycophospholipid. Glycobiology 8, 761–770.[CrossRef]
    [Google Scholar]
  6. Caro, L. H., Tettelin, H., Vossen, J. H., Ram, A. F., van den Ende, H. & Klis, F. M. ( 1997; ). In silico identification of glycosyl-phosphatidylinositol-anchored plasma-membrane and cell wall proteins of Saccharomyces cerevisiae. Yeast 13, 1477–1489.[CrossRef]
    [Google Scholar]
  7. Christianson, T. W., Sikorski, R. S., Dante, M., Shero, J. H. & Hieter, P. ( 1992; ). Multifunctional yeast high-copy-number shuttle vectors. Gene 110, 119–122.[CrossRef]
    [Google Scholar]
  8. Colussi, P. A. & Orlean, P. ( 1997; ). The essential Schizosaccharomyces pombe gpi1 + gene complements a bakers' yeast GPI anchoring mutant and is required for efficient cell separation. Yeast 13, 139–150.[CrossRef]
    [Google Scholar]
  9. Cormack, B. P., Ghori, N. & Falkow, S. ( 1999; ). An adhesin of the yeast pathogen Candida glabrata mediating adherence to human epithelial cells. Science 285, 578–582.[CrossRef]
    [Google Scholar]
  10. De Backer, M. D., Maes, D., Vandoninck, S., Logghe, M., Contreras, R. & Luyten, W. H. ( 1999; ). Transformation of Candida albicans by electroporation. Yeast 15, 1609–1618.[CrossRef]
    [Google Scholar]
  11. De Groot, P. W., Hellingwerf, K. J. & Klis, F. M. ( 2003; ). Genome-wide identification of fungal GPI proteins. Yeast 20, 781–796.[CrossRef]
    [Google Scholar]
  12. De Nobel, H. & Lipke, P. N. ( 1994; ). Is there a role for GPIs in yeast cell-wall assembly? Trends Cell Biol 4, 42–45.[CrossRef]
    [Google Scholar]
  13. De Sampaio, G., Bourdineaud, J. P. & Lauquin, G. J. ( 1999; ). A constitutive role for GPI anchors in Saccharomyces cerevisiae: cell wall targeting. Mol Microbiol 34, 247–256.[CrossRef]
    [Google Scholar]
  14. Doering, T. L. & Schekman, R. ( 1996; ). GPI anchor attachment is required for Gas1p transport from the endoplasmic reticulum in COP II vesicles. EMBO J 15, 182–191.
    [Google Scholar]
  15. Fankhauser, C., Homans, S. W., Thomas-Oates, J. E., McConville, M. J., Desponds, C., Conzelmann, A. & Ferguson, M. A. ( 1993; ). Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces cerevisiae. J Biol Chem 268, 26365–26374.
    [Google Scholar]
  16. Fontaine, T., Magnin, T., Melhert, A., Lamont, D., Latge, J. P. & Ferguson, M. A. ( 2003; ). Structures of the glycosylphosphatidylinositol membrane anchors from Aspergillus fumigatus membrane proteins. Glycobiology 13, 169–177.[CrossRef]
    [Google Scholar]
  17. Fonzi, W. A. ( 1999; ). PHR1 and PHR2 of Candida albicans encode putative glycosidases required for proper cross-linking of β-1,3- and β-1,6-glucans. J Bacteriol 181, 7070–7079.
    [Google Scholar]
  18. Fonzi, W. A. & Irwin, M. Y. ( 1993; ). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717–728.
    [Google Scholar]
  19. Fujii, T., Shimoi, H. & Iimura, Y. ( 1999; ). Structure of the glucan-binding sugar chain of Tip1p, a cell wall protein of Saccharomyces cerevisiae. Biochim Biophys Acta 1427, 133–144.[CrossRef]
    [Google Scholar]
  20. Grimme, S. J., Westfall, B. A., Wiedman, J. M., Taron, C. H. & Orlean, P. ( 2001; ). The essential Smp3 protein is required for addition of the side-branching fourth mannose during assembly of yeast glycosylphosphatidylinositols. J Biol Chem 276, 27731–27739.[CrossRef]
    [Google Scholar]
  21. Hamada, K., Fukuchi, S., Arisawa, M., Baba, M. & Kitada, K. ( 1998; ). Screening for glycosylphosphatidylinositol (GPI)-dependent cell wall proteins in Saccharomyces cerevisiae. Mol Gen Genet 258, 53–59.[CrossRef]
    [Google Scholar]
  22. Hamada, K., Terashima, H., Arisawa, M., Yabuki, N. & Kitada, K. ( 1999; ). Amino acid residues in the omega-minus region participate in cellular localization of yeast glycosylphosphatidylinositol-attached proteins. J Bacteriol 181, 3886–3889.
    [Google Scholar]
  23. Hirose, S., Prince, G. M., Sevlever, D., Ravi, L., Rosenberry, T. L., Ueda, E. & Medof, M. E. ( 1992; ). Characterization of putative glycoinositol phospholipid anchor precursors in mammalian cells. Localization of phosphoethanolamine. J Biol Chem 267, 16968–16974.
    [Google Scholar]
  24. Homans, S. W., Ferguson, M. A., Dwek, R. A., Rademacher, T. W., Anand, R. & Williams, A. F. ( 1988; ). Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein. Nature 333, 269–272.[CrossRef]
    [Google Scholar]
  25. Hong, Y., Maeda, Y., Watanabe, R., Inoue, N., Ohishi, K. & Kinoshita, T. ( 2000; ). Requirement of PIG-F and PIG-O for transferring phosphoethanolamine to the third mannose in glycosylphosphatidylinositol. J Biol Chem 275, 20911–20919.[CrossRef]
    [Google Scholar]
  26. Hoyer, L. L. ( 2001; ). The ALS gene family of Candida albicans. Trends Microbiol 9, 176–180.[CrossRef]
    [Google Scholar]
  27. Kamitani, T., Menon, A. K., Hallaq, Y., Warren, C. D. & Yeh, E. T. ( 1992; ). Complexity of ethanolamine phosphate addition in the biosynthesis of glycosylphosphatidylinositol anchors in mammalian cells. J Biol Chem 267, 24611–24619.
    [Google Scholar]
  28. Kapteyn, J. C., Montijn, R. C., Vink, E., de la Cruz, J., Llobell, A., Douwes, J. E., Shimoi, H., Lipke, P. N. & Klis, F. M. ( 1996; ). Retention of Saccharomyces cerevisiae cell wall proteins through a phosphodiester-linked β-1,3-/β-1,6-glucan heteropolymer. Glycobiology 6, 337–345.[CrossRef]
    [Google Scholar]
  29. Kyte, J. & Doolittle, R. F. ( 1982; ). A simple method for displaying the hydropathic character of a protein. J Mol Biol 157, 105–132.[CrossRef]
    [Google Scholar]
  30. Lee, S. A., Wormsley, S., Kamoun, S., Lee, A. F., Joiner, K. & Wong, B. ( 2003; ). An analysis of the Candida albicans genome database for soluble secreted proteins using computer-based prediction algorithms. Yeast 20, 595–610.[CrossRef]
    [Google Scholar]
  31. Leidich, S. D. & Orlean, P. ( 1996; ). Gpi1, a Saccharomyces cerevisiae protein that participates in the first step in glycosylphosphatidylinositol anchor synthesis. J Biol Chem 271, 27829–27837.[CrossRef]
    [Google Scholar]
  32. Leidich, S. D., Drapp, D. A. & Orlean, P. ( 1994; ). A conditionally lethal yeast mutant blocked at the first step in glycosyl phosphatidylinositol anchor synthesis. J Biol Chem 269, 10193–10196.
    [Google Scholar]
  33. Leidich, S. D., Kostova, Z., Latek, R. R., Costello, L. C., Drapp, D. A., Gray, W., Fassler, J. S. & 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, 13029–13035.[CrossRef]
    [Google Scholar]
  34. Ling, M., Merante, F. & Robinson, B. H. ( 1995; ). A rapid and reliable DNA preparation method for screening a large number of yeast clones by polymerase chain reaction. Nucleic Acids Res 23, 4924–4925.[CrossRef]
    [Google Scholar]
  35. Lu, C. F., Kurjan, J. & Lipke, P. N. ( 1994; ). A pathway for cell wall anchorage of Saccharomyces cerevisiae alpha-agglutinin. Mol Cell Biol 14, 4825–4833.
    [Google Scholar]
  36. McConville, M. J. & Ferguson, M. A. ( 1993; ). The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem J 294, 305–324.
    [Google Scholar]
  37. Mohney, R. P., Knez, J. J., Ravi, L., Sevlever, D., Rosenberry, T. L., Hirose, S. & Medof, M. E. ( 1994; ). Glycoinositol phospholipid anchor-defective K562 mutants with biochemical lesions distinct from those in Thy-1-murine lymphoma mutants. J Biol Chem 269, 6536–6542.
    [Google Scholar]
  38. Mouyna, I., Fontaine, T., Vai, M., Monod, M., Fonzi, W. A., Diaquin, M., Popolo, L., Hartland, R. P. & Latge, J. P. ( 2000; ). Glycosylphosphatidylinositol-anchored glucanosyltransferases play an active role in the biosynthesis of the fungal cell wall. J Biol Chem 275, 14882–14889.[CrossRef]
    [Google Scholar]
  39. Munro, C. A., Winter, K., Buchan, A., Henry, K., Becker, J. M., Brown, A. J., Bulawa, C. E. & Gow, N. A. ( 2001; ). Chs1 of Candida albicans is an essential chitin synthase required for synthesis of the septum and for cell integrity. Mol Microbiol 39, 1414–1426.
    [Google Scholar]
  40. Nuoffer, C., Horvath, A. & Riezman, H. ( 1993; ). Analysis of the sequence requirements for glycosylphosphatidylinositol anchoring of Saccharomyces cerevisiae Gas1 protein. J Biol Chem 268, 10558–10563.
    [Google Scholar]
  41. Ohishi, K., Inoue, N., Maeda, Y., Takeda, J., Riezman, H. & Kinoshita, T. ( 2000; ). Gaa1p and gpi8p are components of a glycosylphosphatidylinositol (GPI) transamidase that mediates attachment of GPI to proteins. Mol Biol Cell 11, 1523–1533.[CrossRef]
    [Google Scholar]
  42. Orlean, P. ( 1997; ). Biogenesis of yeast wall and surface components. In The Molecular and Cellular Biology of the Yeast Saccharomyces: Cell Cycle and Cell Biology, pp. 229–362. Edited by J. R. Pringle, J. R. Broach & E. W. Jones. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory.
  43. Popolo, L. & Vai, M. ( 1998; ). Defects in assembly of the extracellular matrix are responsible for altered morphogenesis of a Candida albicans phr1 mutant. J Bacteriol 180, 163–166.
    [Google Scholar]
  44. Popolo, L., Gilardelli, D., Bonfante, P. & Vai, M. ( 1997; ). Increase in chitin as an essential response to defects in assembly of cell wall polymers in the ggp1Δ mutant of Saccharomyces cerevisiae. J Bacteriol 179, 463–469.
    [Google Scholar]
  45. Ram, A. F., Wolters, A., Ten Hoopen, R. & Klis, F. M. ( 1994; ). A new approach for isolating cell wall mutants in Saccharomyces cerevisiae by screening for hypersensitivity to calcofluor white. Yeast 10, 1019–1030.[CrossRef]
    [Google Scholar]
  46. Ram, A. F., Kapteyn, J. C., Montijn, R. C., Caro, L. H., Douwes, J. E., Baginsky, W., Mazur, P., van den Ende, H. & Klis, F. M. ( 1998; ). Loss of the plasma membrane-bound protein Gas1p in Saccharomyces cerevisiae results in the release of β1,3-glucan into the medium and induces a compensation mechanism to ensure cell wall integrity. J Bacteriol 180, 1418–1424.
    [Google Scholar]
  47. Richard, M., De Groot, P., Courtin, O., Poulain, D., Klis, F. & Gaillardin, C. ( 2002a; ). GPI7 affects cell-wall protein anchorage in Saccharomyces cerevisiae and Candida albicans. Microbiology 148, 2125–2133.
    [Google Scholar]
  48. Richard, M., Ibata-Ombetta, S., Dromer, F., Bordon-Pallier, F., Jouault, T. & Gaillardin, C. ( 2002b; ). Complete glycosylphosphatidylinositol anchors are required in Candida albicans for full morphogenesis, virulence and resistance to macrophages. Mol Microbiol 44, 841–853.[CrossRef]
    [Google Scholar]
  49. Roberts, W. L., Santikarn, S., Reinhold, V. N. & Rosenberry, T. L. ( 1988; ). Structural characterization of the glycoinositol phospholipid membrane anchor of human erythrocyte acetylcholinesterase by fast atom bombardment mass spectrometry. J Biol Chem 263, 18776–18784.
    [Google Scholar]
  50. Sherman, F. ( 1991; ). Getting started with yeast. Methods Enzymol 194, 3–21.
    [Google Scholar]
  51. Sikorski, R. S. & Hieter, P. ( 1989; ). A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics 122, 19–27.
    [Google Scholar]
  52. Smith, T. K., Sharma, D. K., Crossman, A., Dix, A., Brimacombe, J. S. & Ferguson, M. A. ( 1997; ). Parasite and mammalian GPI biosynthetic pathways can be distinguished using synthetic substrate analogues. EMBO J 16, 6667–6675.[CrossRef]
    [Google Scholar]
  53. Staab, J. F., Bradway, S. D., Fidel, P. L. & Sundstrom, P. ( 1999; ). Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283, 1535–1538.[CrossRef]
    [Google Scholar]
  54. Stahl, N., Baldwin, M. A., Hecker, R., Pan, K. M., Burlingame, A. L. & Prusiner, S. B. ( 1992; ). Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid. Biochemistry 31, 5043–5053.[CrossRef]
    [Google Scholar]
  55. Sundstrom, P. ( 2002; ). Adhesion in Candida spp. Cell Microbiol 4, 461–469.[CrossRef]
    [Google Scholar]
  56. Sütterlin, C., Horvath, A., Gerold, P., Schwarz, R. T., Wang, Y., Dreyfuss, M. & Riezman, H. ( 1997; ). Identification of a species-specific inhibitor of glycosylphosphatidylinositol synthesis. EMBO J 16, 6374–6383.[CrossRef]
    [Google Scholar]
  57. Taron, C. H., Wiedman, J. M., Grimme, S. J. & Orlean, P. ( 2000; ). Glycosylphosphatidylinositol biosynthesis defects in Gpi11p- and Gpi13p-deficient yeast suggest a branched pathway and implicate gpi13p in phosphoethanolamine transfer to the third mannose. Mol Biol Cell 11, 1611–1630.[CrossRef]
    [Google Scholar]
  58. Taron, B. W., Colussi, P. A., Wiedman, J. M., Orlean, P. & Taron, C. H. ( 2004; ). Human Smp3p adds a fourth mannose to yeast and human glycosylphosphatidylinositol precursors in vivo. J Biol Chem doi: 10.1074/jbc.M405081200.
    [Google Scholar]
  59. Tsukahara, K., Hata, K., Nakamoto, K. & 9 other authors ( 2003; ). Medicinal genetics approach towards identifying the molecular target of a novel inhibitor of fungal cell wall assembly. Mol Microbiol 48, 1029–1042.[CrossRef]
    [Google Scholar]
  60. Vossen, J. H., Ram, A. F. & Klis, F. M. ( 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, 549–551.[CrossRef]
    [Google Scholar]
  61. Vossen, J. H., Muller, W. H., Lipke, P. N. & Klis, F. M. ( 1997; ). Restrictive glycosylphosphatidylinositol anchor synthesis in cwh6/gpi3 yeast cells causes aberrant biogenesis of cell wall proteins. J Bacteriol 179, 2202–2209.
    [Google Scholar]
  62. Zaragoza, O., de Virgilio, C., Ponton, J. & Gancedo, C. ( 2002; ). Disruption in Candida albicans of the TPS2 gene encoding trehalose-6-phosphate phosphatase affects cell integrity and decreases infectivity. Microbiology 148, 1281–1290.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.27254-0
Loading
/content/journal/micro/10.1099/mic.0.27254-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error