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Genetic analysis of Hsp70 phosphorylation sitesreveals a role in Candida albicanscell and colony morphogenesis

ABSTRACT: Heat shock proteins are best known for their role as chaperonins involved in general proteostasis, but they can also participate in specific cellular regulatory pathways, e.g. via their post-translational modification. Hsp70/Ssa1 is a central cytoplasmic chaperonin in eukaryotes, which also participates in cell cycle regulation via its phosphorylation at a specific residue. 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 8were only detected in the hyphalcells. Genetic analysis of these sites revealedallele-specific effects on growth at high temperature, cell and colony morphology, and resistance to cell wall-active drugs.This analysis could help direct screens for Ssa1-specific drugs to combat C. albicans virulence.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 suggests 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, consistent with the “chaperone code” hypothesis.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Candida Albicans (yeast)

SUBMITTER: Donald Wolfgeher

LAB HEAD: Dr. Daniel Kornitzer

PROVIDER: PXD010827 | Pride | 2018-11-21

REPOSITORIES: Pride

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