Srg1, a putative protein phosphatase from the HAD-family, is involved in stress adaptation in Candida albicans

Abstract

BackgroundThe cell stress response plays an important role in the survival of organisms. Studies have revealed that the pathogenic yeast Candida albicans that constantly encounters various environmental insults inside the host has emerged as an ideal system to understand the molecular mechanism (s) of stress response. In this study, we characterize a stress-inducible gene SRG1 which is a Halo Acid Dehalogenase (HAD) family member from C. albicans. MethodsWe used confocal microscopy, site-directed mutagenesis, gene deletion techniques, and tandem-affinity purification and co-immunoprecipitation studies to functionally characterize SRG1. ResultsThe sub-cellular localization of Srg1 is predominantly cytoplasmic and includes punctate mitochondrial staining in the presence of salt. Protein purification studies coupled with LC-MS analysis showed that Srg1 is a phosphoprotein. The Srg1 mutant carrying S47A and S49A mutations failed to migrate to mitochondria in the presence of salt but retained its phosphatase activity. Srg1 migrates to the nucleus in ∆hog1 mutant cells indicating an unorthodox role for HAD family proteins in stress-mediated transcriptional response. Srg1 also interacts with Erg13, a component involved in the mitochondrial membrane lipid biosynthesis pathway. ConclusionsA multistep relay mechanism that includes a positive modulation by the MAP kinase Hog1 and a negative modulation by the global repressor Tup1 controls SRG1 expression. General significanceTaken together, our work contributes towards gaining a functional insight into a class of phosphatases that probably have evolved with novel specificities in the pathogenic yeast C. albicans to counteract stressful conditions.