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Eukaryotic Cell, August 2005, p. 1364-1374, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1364-1374.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Yapsins Are a Family of Aspartyl Proteases Required for Cell Wall Integrity in Saccharomyces cerevisiae

Damian J. Krysan,1* Elizabeth L. Ting,2 Claudia Abeijon,2 Lee Kroos,3 and Robert S. Fuller4*

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{Delta}2{Delta} mutant and the quintuple yapsin mutant (5yps{Delta}) undergo osmoremedial cell lysis at 37°C. The cell walls of both 5yps{Delta} and yps1{Delta}2{Delta} 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{Delta} 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{Delta}. 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{Delta} 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.

* Corresponding author. Mailing address for Damian J. Krysan: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642. Phone: (585) 275-5944. Fax: (585) 756-7780. E-mail: damian_krysan{at}urmac.rochester.edu. Mailing address for Robert S. Fuller: Department of Biological Chemistry, University of Michigan Medical School, 5413 Medical Science Building I, 1303 East Catherine Street, Ann Arbor, MI 48109. Phone: (734) 936-9764. Fax: (734) 763-7799. E-mail: bfuller{at}umich.edu.

Eukaryotic Cell, August 2005, p. 1364-1374, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1364-1374.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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