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Department of Pediatrics and Communicable Diseases, Division of Pediatric Infectious Disease, University of Michigan Hospitals,1 Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109,4 Department of Molecular and Cell Biology, Goldman School of Dental Medicine, Boston University, Boston, Massachusetts 02118,2 Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 488243
Received 6 May 2005/ Accepted 9 June 2005
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 yps1
2
mutant and the quintuple yapsin mutant (5yps
) undergo osmoremedial cell lysis at 37°C. The cell walls of both 5yps
and yps1
2
mutants have decreased amounts of 1,3- and 1,6-ß-glucan. Although there is decreased incorporation of both 1,3- and 1,6-ß-glucan in the 5yps
mutant in vivo, in vitro specific activity of both 1,3- and 1,6-ß-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 5yps
. 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 yps1
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.
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