Functional Characterization Of The CaGDT1 Gene In Candida Albicans

Saccharomyces cerevisiae ScGdt1 and its human homologous transmembrane protein 165(TMEM165), defects of which are associated with Congenital Disorders of Glycosylation, are members of the cation/Ca2+ exchanger superfamily. In this study, we found and defined a new protein CaGdt1 by sequence alignment in Candida albicans. As the functional homolog of ScGdt1, CaGdt1 shows genetic interactions with Ca Pmr1 in response to cell wall stresses by phenotypic screening of gdt1/gdt1 and gdt1/gdt1 pmr1/pmr1 mutant strains. Calcineurin function is required for the growth and the response to cell wall stress, and inhibition of calcineurin promotes the cell death, and disrupts the cell wall and vacuolar integrity, of Candida albicans cells lacking both CaGDT1 and CaPMR1. Deletion of CaGDT1 and/or CaPMR1 increases the calcium uptake and activates the calcium/calcineurin signaling in response to calcium stress. Deletion of CaPMR1 leads to the up-regulation of CaPMC1 expression, while deletion of CaGDT1 elevates the CaVCX1 expression. In addition, CaGdt1 plays a role in the CaCek1-mediated, but not Ca Mkc1-mediated, cell wall integrity signaling in a cell wall stress-independent fashion. CaGdt1 is localized in the Golgi apparatus but at distinct sites from CaPmr1. Furthermore, deletion of CaGDT1 leads to filamentation defect, and increases the flocculation rate, of cells lacking CaPMR1. CaGdt1 is partially involved in the virulence of C. albicans in a mouse model of systemic candidasis.