Yapsins are a family of aspartyl proteases required for cell wall integrity in Saccharomyces cerevisiae.

Damian J Krysan, Elizabeth L Ting, Claudia Abeijon, Lee Kroos, Robert S Fuller
Author Information
  1. Damian J Krysan: Division of Pediatric Infectious Disease, Department of Pediatrics and Communicable Diseases, University of Michigan Hospitals, Ann Arbor, Michigan 48109, USA. damian_krysan@urmac.rochester.edu

Abstract

The yeast cell wall is a crucial extracellular organelle that protects the cell from lysis during environmental stress and morphogenesis. Here, we demonstrate that the yapsin family of five glycosylphosphatidylinositol-linked aspartyl proteases is required for cell wall integrity in Saccharomyces cerevisiae. Yapsin null mutants show hypersensitivity to cell wall perturbation, and both the yps1Delta2Delta mutant and the quintuple yapsin mutant (5ypsDelta) undergo osmoremedial cell lysis at 37 degrees C. The cell walls of both 5ypsDelta and yps1Delta2Delta mutants have decreased amounts of 1,3- and 1,6-beta-glucan. Although there is decreased incorporation of both 1,3- and 1,6-beta-glucan in the 5ypsDelta mutant in vivo, in vitro specific activity of both 1,3- and 1,6-beta-glucan synthesis is similar to wild type, indicating that the yapsins affect processes downstream of glucan synthesis and that the yapsins may be involved in the incorporation or retention of cell wall glucan. Presumably as a response to the significant alterations in cell wall composition, the cell wall integrity mitogen-activated kinase signaling cascade (PKC1-MPK pathway) is basally active in 5ypsDelta. YPS1 expression is induced during cell wall stress and remodeling in a PKC1-MPK1-dependent manner, indicating that Yps1p is a direct, and important, output of the cell wall integrity response. The Candida albicans (SAP9) and Candida glabrata (CgYPS1) homologues of YPS1 complement the phenotypes of the yps1Delta mutant. Taken together, these data indicate that the yapsins play an important role in glucan homeostasis in S. cerevisiae and that yapsin homologues may play a similar role in the pathogenic yeasts C. albicans and C. glabrata.

References

  1. J Bacteriol. 1999 Jul;181(13):3886-9 [PMID: 10383953]
  2. J Antimicrob Chemother. 2005 May;55(5):645-54 [PMID: 15820985]
  3. Microbiol Mol Biol Rev. 2003 Sep;67(3):400-28, table of contents [PMID: 12966142]
  4. Yeast. 1999 Jul;15(10A):813-20 [PMID: 10407261]
  5. Yeast. 1994 Aug;10(8):1019-30 [PMID: 7992502]
  6. Biochim Biophys Acta. 1997 Nov 27;1359(2):110-22 [PMID: 9409808]
  7. Microbiology (Reading). 1994 Sep;140 ( Pt 9):2239-46 [PMID: 7952175]
  8. Microbiology (Reading). 2004 Oct;150(Pt 10):3197-208 [PMID: 15470100]
  9. Yeast. 2004 Oct 15;21(13):1121-31 [PMID: 15484287]
  10. Mol Microbiol. 2002 Jun;44(5):1167-83 [PMID: 12068804]
  11. Mol Cell Biol. 1994 Feb;14(2):1017-25 [PMID: 8289782]
  12. Gene. 2002 May 1;289(1-2):177-84 [PMID: 12036596]
  13. Curr Genet. 2002 Sep;41(6):367-78 [PMID: 12228806]
  14. Genes Dev. 1997 Dec 15;11(24):3432-44 [PMID: 9407035]
  15. Microbiol Rev. 1995 Sep;59(3):345-86 [PMID: 7565410]
  16. Mol Microbiol. 1999 Dec;34(5):1049-57 [PMID: 10594829]
  17. Antimicrob Agents Chemother. 2002 Aug;46(8):2462-9 [PMID: 12121919]
  18. Mol Microbiol. 2003 Jul;49(1):23-35 [PMID: 12823808]
  19. Traffic. 2001 Dec;2(12):896-907 [PMID: 11737827]
  20. Chem Rev. 2002 Dec;102(12):4525-48 [PMID: 12475200]
  21. Gene. 1986;45(3):299-310 [PMID: 3026915]
  22. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10752-6 [PMID: 7479877]
  23. Mol Microbiol. 2002 Nov;46(3):781-9 [PMID: 12410835]
  24. Mol Cell Biol. 1998 Feb;18(2):1013-22 [PMID: 9447998]
  25. Microbiol Mol Biol Rev. 1998 Dec;62(4):1264-300 [PMID: 9841672]
  26. Genetics. 2004 May;167(1):35-49 [PMID: 15166135]
  27. J Biol Chem. 2003 Feb 21;278(8):5523-30 [PMID: 12468548]
  28. J Biol Chem. 2004 Apr 9;279(15):15183-95 [PMID: 14739279]
  29. Microbiology (Reading). 2001 Apr;147(Pt 4):781-794 [PMID: 11283274]
  30. Yeast. 2002 Jun 15;19(8):671-90 [PMID: 12185837]
  31. Mol Microbiol. 1999 May;32(4):671-80 [PMID: 10361272]
  32. Nature. 2004 Jul 1;430(6995):35-44 [PMID: 15229592]
  33. Yeast. 1990 Mar-Apr;6(2):127-37 [PMID: 2183521]
  34. J Biol Chem. 2003 Sep 12;278(37):34998-5015 [PMID: 12824174]
  35. Microbiology (Reading). 1998 Oct;144 ( Pt 10):2731-2737 [PMID: 9802014]
  36. J Biol Chem. 1998 Nov 27;273(48):31648-51 [PMID: 9822624]
  37. FEMS Microbiol Rev. 2002 Aug;26(3):239-56 [PMID: 12165426]
  38. Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10287-92 [PMID: 12928491]
  39. J Biol Chem. 1996 Feb 23;271(8):4168-76 [PMID: 8626758]
  40. Genetics. 2000 Jul;155(3):1005-18 [PMID: 10880465]
  41. J Bacteriol. 1998 Oct;180(19):5030-7 [PMID: 9748433]
  42. Science. 2004 Feb 6;303(5659):808-13 [PMID: 14764870]
  43. Mol Biol Cell. 2000 Dec;11(12):4241-57 [PMID: 11102521]
  44. J Biol Chem. 1999 Aug 20;274(34):24431-7 [PMID: 10446224]
  45. Biochemistry. 1998 Mar 3;37(9):2768-77 [PMID: 9485427]
  46. Anal Biochem. 2002 Feb 1;301(1):136-50 [PMID: 11811978]
  47. Arch Microbiol. 1992;158(2):115-26 [PMID: 1417414]
  48. Biochim Biophys Acta. 1999 Jan 6;1426(2):373-83 [PMID: 9878836]
  49. Med Mycol. 2001;39 Suppl 1:55-66 [PMID: 11800269]
  50. Microbiology (Reading). 2000 Sep;146 ( Pt 9):2121-2132 [PMID: 10974100]
  51. Cell. 2000 Jul 7;102(1):109-26 [PMID: 10929718]
  52. Methods Enzymol. 2002;350:112-31 [PMID: 12073308]
  53. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12679-84 [PMID: 10535982]
  54. Mol Gen Genet. 2000 Sep;264(1-2):64-74 [PMID: 11016834]
  55. Genetics. 2003 Mar;163(3):875-94 [PMID: 12663529]
  56. Genes Dev. 1995 Jul 1;9(13):1559-71 [PMID: 7628692]
  57. Mol Cell Biol. 2001 Apr;21(7):2449-62 [PMID: 11259593]
  58. J Biol Chem. 1995 Sep 1;270(35):20847-54 [PMID: 7657670]
  59. J Cell Biol. 2002 Sep 2;158(5):885-900 [PMID: 12196508]
  60. Mol Microbiol. 2003 Nov;50(3):883-96 [PMID: 14617149]
  61. FEBS Lett. 1990 Jul 30;268(1):99-102 [PMID: 2116982]
  62. Biochem J. 1999 Apr 15;339 ( Pt 2):407-11 [PMID: 10191273]
  63. Cell. 2004 Jan 9;116(1):121-37 [PMID: 14718172]
  64. Mol Biol Cell. 2001 Feb;12(2):323-37 [PMID: 11179418]

Grants

  1. R01 GM039697/NIGMS NIH HHS
  2. R01 GM043585/NIGMS NIH HHS
  3. R01 GM059773/NIGMS NIH HHS
  4. T32 HD007513/NICHD NIH HHS
  5. GM43585/NIGMS NIH HHS
  6. R01 GM39697/NIGMS NIH HHS
  7. R01 GM59773/NIGMS NIH HHS

MeSH Term

Aspartic Acid Endopeptidases
Calcineurin
Candida albicans
Candida glabrata
Caspofungin
Cell Wall
Echinocandins
Glucans
Lipopeptides
Mitogen-Activated Protein Kinases
Peptides, Cyclic
Protein Kinase C
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Temperature

Chemicals

Echinocandins
Glucans
Lipopeptides
Peptides, Cyclic
Saccharomyces cerevisiae Proteins
PKC1 protein, S cerevisiae
Protein Kinase C
Mitogen-Activated Protein Kinases
SLT2 protein, S cerevisiae
Calcineurin
Aspartic Acid Endopeptidases
YPS1 protein, S cerevisiae
Caspofungin

Word Cloud

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