Genetic analysis of Hsp70 phosphorylation sites reveals a role in Candida albicans cell and colony morphogenesis
Heat shock proteins are best known for their role as chaperonins involved in protein folding, but they can also participate in cellular regulatory pathways, e.g. via their phosphorylation. Hsp70/Ssa1 is a central cytoplasmic chaperonin in eukaryotes, which was shown to participate i.a. in cell cycle regulation in the yeast Saccharomyces cerevisiae. Here we analyze the role of Ssa1 phosphorylation in the morphogenesis of the fungus Candida albicans, a common human opportunistic pathogen. C. albicans can assume alternative yeast and hyphal (mold) morphologies, an ability that contributes to its virulence. We identified 11 phosphorylation sites on C. albicans Ssa1, of which 8 were only detected in the hyphal cells. Genetic analysis of 10 of these sites revealed allele-specific effects on growth at high temperature, cell and colony morphology, and resistance to cell wall-active drugs. The pleiotropic effects of many Ssa1 mutations are consistent with the large number of Ssa1 client proteins, whereas the lack of concordance between the phenotypes of the different alleles are consistent with the possibility that different sites on Ssa1 can affect interaction with specific classes of client protein, and that modification of these sites can play cellular regulatory roles.