Glycosylphosphatidylinositol (GPI)-linked aspartyl proteases regulate vacuole homeostasis in Candida glabrata

A family of eleven glycosylphosphatidylinositol (GPI)-linked, cell surface-associated aspartyl proteases (yapsins)in a human opportunistic fungal pathogen Candida glabrata is required for cell wall remodeling and pH homeostasis, survival in macrophages and virulence in a murine model of disseminated candidiasis. Here, we report new roles for yapsins in C. glabrata physiology and implicate them for the first time in the regulation of vacuole homeostasis. We show that a C. glabrata mutant lacking all eleven yapsins, Cgyps1-11∆, possesses an enlarged vacuole and displays vma- (vacuolar membrane ATPase)-like phenotypes with elevated metal ion susceptibility in alkaline pH medium and diminished Vma activity. Our data also demonstrate a singular role for CgYps1 in the maintenance of ion homeostasis under normal and calcineurin-inhibited conditions. Elevated polyphosphate levels and diminished cellular CPY activity in Cgyps1-11∆ mutant highlight the yapsin requirement for a properly functioning vacuole. Lastly, a gross perturbation of cellular homeostasis in Cgyps1-11∆ mutant, even in the absence of external stressors, characterized by reduced levels of ATP and stress metabolites, elevated reactive oxygen species levels, cell surface abnormalities and constitutively activated protein kinase C signaling pathway, underscore diverse physiological functions of yapsins in C. glabrata.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research