Derepressed hyphal growth and reduced virulence in a VH1 family-related protein phosphatase mutant of the human pathogen Candida albicans

被引:92
作者
Csank, C
Makris, C
Meloche, S
Schroppel, K
Rollinghoff, M
Dignard, D
Thomas, DY
Whiteway, M
机构
[1] NATL RES COUNCIL CANADA, BIOTECHNOL RES INST, EUKARYOT GENET GRP, MONTREAL, PQ H4P 2R2, CANADA
[2] HOP HOTEL DIEU, CTR RECH, MONTREAL, PQ H2W 1T8, CANADA
[3] UNIV MONTREAL, DEPT PHARMACOL, MONTREAL, PQ H2W 1T8, CANADA
[4] UNIV ERLANGEN NURNBERG, INST CLIN MICROBIOL & IMMUNOL, D-91054 ERLANGEN, GERMANY
[5] MCGILL UNIV, DEPT BIOL, MONTREAL, PQ H3A 1B1, CANADA
关键词
D O I
10.1091/mbc.8.12.2539
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Mitogen-activated protein (MAP) kinases are pivotal components of eukaryotic signaling cascades. Phosphorylation of tyrosine and threonine residues activates MAP kinases, but either dual-specificity or monospecificity phosphatases can inactivate them. The Candida albicans CPP1 gene, a structural member of the VH1 family of dual-specificity phosphatases, was previously cloned by its ability to block the pheromone response MAP kinase cascade in Saccharomyces cerevisiae. Cpp1p inactivated mammalian MAP kinases in vitro and acted as a tyrosine-specific enzyme. In C. albicans a MAP kinase cascade can trigger the transition from the budding yeast form to a more invasive filamentous form. Disruption of the CPP1 gene in C. albicans derepressed the yeast to hyphal transition at ambient temperatures, on solid surfaces. A hyphal growth rate defect under physiological conditions in vitro was also observed and could explain a reduction in virulence associated with reduced fungal burden in the kidneys seen in a systemic mouse model. A hyper-hyphal pathway may thus have some detrimental effects on C. albicans cells. Disruption of the MAP kinase homologue CEK1 suppressed the morphological effects of the CPP1 disruption in C. albicans. The results presented here demonstrate the biological importance of a tyrosine phosphatase in cell-fate decisions and virulence in C. albicans.
引用
收藏
页码:2539 / 2551
页数:13
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