1887

Abstract

is able to grow in a variety of reversible morphological forms (yeast, pseudohyphal and hyphal) in response to various environmental signals, noteworthy among them being -acetylglucosamine (GlcNAc). The gene , homologous to , which encodes the general amino acid permease from , was isolated on the basis of its induction by GlcNAc through differential screening of a genomic library. The gene could functionally complement an mutant by rendering it susceptible to the toxic amino acid analogue mimosine in minimal proline media. As in , mutation of the gene had an effect on citrulline uptake in . Northern analysis showed that GlcNAc-induced expression of was further enhanced in synthetic minimal media supplemented with single amino acids (glutamate, proline and glutamine) or urea (without amino acids) but repressed in minimal ammonium media. Induction of expression by GlcNAc was nullified in deleted for the transcription factor and the hyphal regulator , indicating the involvement of Cph1p-dependent Ras1p signalling in expression. A homozygous mutant of this gene showed defective hyphal formation in solid hyphal-inducing media and exhibited less hyphal clumps when induced by GlcNAc. Alteration of morphology and short filamentation under nitrogen-starvation conditions in the heterozygous mutant suggested that affects morphogenesis in a dose-dependent manner.

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2003-09-01
2019-10-22
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References

  1. Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A. & Struhl, K. ( 1994; ). Current Protocols in Molecular Biology. New York: Wiley.
  2. Bernard, F. & Andre, B. ( 2001; ). Ubiquitin and SCFGrr1 ubiquitin ligase complex are involved in the signalling pathway activated by external amino acids in Saccharomyces cerevisiae. FEBS Lett 496, 81–85.[CrossRef]
    [Google Scholar]
  3. Blinder, D., Coschigano, P. W. & Magasanik, B. ( 1996; ). Interaction of GATA factor Gln3p with the nitrogen regulator Ure2p in Saccharomyces cerevisiae. J Bacteriol 178, 4734–4736.
    [Google Scholar]
  4. Bockmuhl, D. P., Krishnamurthy, S., Gerads, M., Sonneborn, A. & Ernst, J. F. ( 2001; ). Distinct and redundant roles of the two protein kinase A isoforms Tpk1p and Tpk2p in morphogenesis and growth of Candida albicans. Mol Microbiol 42, 1243–1257.
    [Google Scholar]
  5. Courchesne, W. E. & Magasanik, B. ( 1983; ). Ammonia regulation of amino acid permease in Saccharomyces cerevisiae. Mol Cell Biol 3, 672–683.
    [Google Scholar]
  6. Csank, C., Schroppel, K., Leberer, E., Harcus, D., Mohamed, O., Meloche, S., Thomas, D. Y. & Whiteway, M. ( 1998; ). Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun 66, 2713–2721.
    [Google Scholar]
  7. Cunningham, T. S. & Cooper, T. G. ( 1993; ). The Saccharomyces cerevisiae DAL80 repressor protein binds to multiple copies of GATAA-containing sequences (URSGATA). J Bacteriol 175, 5851–5861.
    [Google Scholar]
  8. Cutler, F. E. ( 1991; ). Putative virulence factor of Candida albicans. Annu Rev Microbiol 45, 187–218.[CrossRef]
    [Google Scholar]
  9. Feng, Q., Summers, E., Guo, B. & Fink, G. ( 1999; ). Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol 181, 6339–6346.
    [Google Scholar]
  10. Fonzi, W. A. & Irwin, M. Y. ( 1993; ). Isogenic strain construction and gene mapping in Candida albicans. Genetics 134, 717–728.
    [Google Scholar]
  11. Gietz, D., St Jean, A., Woods, R. A. & Schiestl, R. H. ( 1992; ). Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 20, 1425.[CrossRef]
    [Google Scholar]
  12. Grenson, M., Hou, C. & Crabeel, M. ( 1970; ). Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. IV. Evidence for a general amino acid permease. J Bacteriol 3, 770–777.
    [Google Scholar]
  13. Jauniaux, J. C. & Grenson, M. ( 1990; ). GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Eur J Biochem 190, 39–44.[CrossRef]
    [Google Scholar]
  14. Kumar, M. J., Jamaluddin, M. S., Natarajan, K., Kaur, D. & Datta, A. ( 2000; ). The inducible N-acetylglucosamine catabolic pathway gene cluster in Candida albicans: discrete N-acetylglucosamine-inducible factors interact at the promoter of NAG1. Proc Natl Acad Sci U S A 97, 14218–14223.[CrossRef]
    [Google Scholar]
  15. 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]
  16. Leberer, E., Harcus, D., Broadbent, I. D. & 7 other authors ( 1996; ). Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans. Proc Natl Acad Sci U S A 93, 13217–13222.[CrossRef]
    [Google Scholar]
  17. Leberer, E., Ziegelbauer, K., Schmidt, A., Harcus, D., Dignard, D., Ash, J., Johnson, L. & Thomas, D. Y. ( 1997; ). Virulence and hyphal formation of Candida albicans require the Ste20p-like protein kinase CaCla4p. Curr Biol 7, 539–546.[CrossRef]
    [Google Scholar]
  18. Leng, P., Lee, P. R., Wu, H. & Brown, A. J. ( 2001; ). Efg1, a morphogenetic regulator in Candida albicans, is a sequence-specific DNA binding protein. J Bacteriol 183, 4090–4093.[CrossRef]
    [Google Scholar]
  19. Liu, H., Kohler, J. & Fink, G. R. ( 1994; ). Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science 266, 1723–1726.[CrossRef]
    [Google Scholar]
  20. Lodish, H. F. ( 1988; ). Multi-spanning membrane proteins: how accurate are the models? Trends Biochem Sci 13, 332–334.[CrossRef]
    [Google Scholar]
  21. Malathi, K., Ganesan, K. & Datta, A. ( 1994; ). Identification of a putative transcription factor in Candida albicans that can complement the mating defect of Saccharomyces cerevisiae ste12 mutants. J Biol Chem 269, 22945–22951.
    [Google Scholar]
  22. Mattia, E., Carruba, G., Angiolella, L. & Cassone, A. ( 1982; ). Induction of germ tube formation by N-acetyl-d-glucosamine in Candida albicans: uptake of inducer and germination response. J Bacteriol 152, 555–562.
    [Google Scholar]
  23. McCusker, J. H. & Haber, J. E. ( 1990; ). Mutations in Saccharomyces cerevisiae which confer resistance to several amino acid analogues. Mol Cell Biol 10, 2941–2949.
    [Google Scholar]
  24. Miller, S. M. & Magasanik, B. ( 1991; ). Role of the complex upstream region of the GDH2 gene in nitrogen regulation of the NAD-linked glutamate dehydrogenase in Saccharomyces cerevisiae. Mol Cell Biol 12, 6229–6247.
    [Google Scholar]
  25. Odds, F. C. ( 1988; ). Candida and Candidosis: a Review and Bibliography, 2nd edn. London: Baillière Tindall.
  26. Okayama, H., Kawaichi, M., Brownstein, M., Lee, F., Yokota, T. & Arai, K. ( 1987; ). High-efficiency cloning of full-length cDNA: construction and screening of cDNA expression libraries for mammalian cells. Methods Enzymol 154, 3–28.
    [Google Scholar]
  27. Roberg, K. J., Rowley, N. & Kaiser, C. A. ( 1997; ). Physiological regulation of membrane protein sorting late in the secreting pathway of Saccharomyces cerevisiae. J Cell Biol 137, 1469–1482.[CrossRef]
    [Google Scholar]
  28. Rowen, D. W., Esiobu, N. & Magasanik, B. ( 1997; ). Role of GATA factor Nil2p in nitrogen regulation of gene expression in Saccharomyces cerevisiae. J Bacteriol 179, 3761–3766.
    [Google Scholar]
  29. Rytka, J. ( 1975; ). Positive selection of general amino acid permease mutants of Saccharomyces cerevisiae. J Bacteriol 121, 562–570.
    [Google Scholar]
  30. Sambrook, J., Fritsch, E. F. & Maniatis, T. ( 1989; ). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  31. Simonitti, N., Strippoli, V. & Cassone, A. ( 1974; ). Yeast mycelial conversion induced by N-acetyl-d-glucosamine in Candida albicans. Nature 252, 555–562.[CrossRef]
    [Google Scholar]
  32. Singh, P., Ganesan, K., Malathi, K., Ghosh, D. & Datta, A. ( 1994; ). ACPR, a STE12 homologue from Candida albicans, is a strong inducer of pseudohyphae in Saccharomyces cerevisiae haploids and diploids. Biochem Biophys Res Commun 205, 1079–1085.[CrossRef]
    [Google Scholar]
  33. Singh, P., Ghosh, S. & Datta, A. ( 1997; ). A novel MAP-kinase kinase from Candida albicans. Gene 190, 99–104.[CrossRef]
    [Google Scholar]
  34. Singh, P., Ghosh, S. & Datta, A. ( 2001; ). Attenuation of virulence and changes in morphology in Candida albicans by disruption of the N-acetylglucosamine catabolic pathway. Infect Immun 69, 7898–7903.[CrossRef]
    [Google Scholar]
  35. Sonneborn, A., Bockmuhl, D. P., Gerads, M., Kurpanek, K., Sanglard, D. & Ernst, J. F. ( 2000; ). Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol 35, 386–396.[CrossRef]
    [Google Scholar]
  36. Sophianopoulon, V. & Diallionas, G. ( 1995; ). Amino acid transporter of lower eukaryotes; regulation, structure and topogenesis. FEMS Microbiol Rev 16, 53–75.[CrossRef]
    [Google Scholar]
  37. Springael, J. Y. & Andre, B. ( 1998; ). Nitrogen regulated ubiquitination of the Gap1 permease of Saccharomyces cerevisiae. Mol Biol Cell 9, 1253–1263.[CrossRef]
    [Google Scholar]
  38. Stanbrough, M., Rowen, D. W. & Magasanik, B. ( 1995; ). Role of the GATA factors Gln3p and Nil1p of Saccharomyces cerevisiae in the expression of nitrogen regulated genes. Proc Natl Acad Sci U S A 92, 9450–9454.[CrossRef]
    [Google Scholar]
  39. Stoldt, V. R., Sonneborn, A., Leuker, C. E. & Ernst, J. F. ( 1997; ). Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J 16, 1982–1991.[CrossRef]
    [Google Scholar]
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