GPI (glycosylphosphatidylinositol)-linked aspartyl proteases regulate vacuole homoeostasis in Candida glabrata
| Autor: | Rupinder Kaur, Ritu Taigwal, Mubashshir Rasheed, Rosalin Sahoo, Gaurav Bairwa |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Vacuolar Proton-Translocating ATPases
Aspartic Acid Proteases Cell Survival Glycosylphosphatidylinositols ATPase Cell Mutant Candida glabrata Vacuole Biochemistry medicine Homeostasis Humans Molecular Biology Protein kinase C chemistry.chemical_classification Reactive oxygen species biology Cell Biology biology.organism_classification Cell biology medicine.anatomical_structure chemistry Vacuoles biology.protein |
| Zdroj: | Biochemical Journal. 458:323-334 |
| ISSN: | 1470-8728 0264-6021 |
| DOI: | 10.1042/bj20130757 |
| Popis: | A family of 11 GPI (glycosylphosphatidylinositol)-linked cell surface-associated aspartyl proteases (yapsins) in the human opportunistic fungal pathogen Candida glabrata is required for cell wall remodelling, pH homoeostasis, survival in macrophages and virulence in a murine model of disseminated candidiasis. In the present paper, we report new roles for yapsins in C. glabrata physiology and implicate them for the first time in the regulation of vacuole homoeostasis. In the present study we show that a C. glabrata mutant lacking all 11 yapsins, Cgyps1-11∆, possesses an enlarged vacuole and displays vma− (vacuolar membrane ATPase)-like phenotypes with elevated metal ion susceptibility in an alkaline pH medium and diminished Vma activity. The results of the present study also demonstrate a singular role for CgYps1 (C. glabrata yapsin 1) in the maintenance of ion homoeostasis under normal and calcineurin-inhibited conditions. Elevated polyphosphate levels and diminished cellular CPY (carboxypeptidase Y) activity in the Cgyps1-11∆ mutant highlight the yapsin requirement for a properly functioning vacuole. Lastly, a gross perturbation of cellular homoeostasis in the Cgyps1-11∆ mutant, even in the absence of external stressors, characterized by reduced levels of ATP and stress metabolites, elevated ROS (reactive oxygen species) levels, cell surface abnormalities, and a constitutively activated PKC (protein kinase C) signalling pathway underscore diverse physiological functions of yapsins in C. glabrata. |
| Databáze: | OpenAIRE |
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