Reduced TOR signaling sustains hyphal development inCandida albicansby lowering Hog1 basal activity

Abstract

Candida albicans is able to undergo reversible morphological changes between yeast and hyphal forms in response to environmental cues. This morphological plasticity is essential for its pathogenesis. Hyphal development requires two temporally linked changes in promoter chromatin, which is sequentially regulated by temporarily clearing the transcription inhibitor Nrg1 upon activation of cAMP/protein kinase A and promoter recruitment of the histone deacetylase Hda1 under reduced target of rapamycin (Tor1) signaling. The GATA family transcription factor Brg1 recruits Hda1 to promoters for sustained hyphal development, and BRG1 expression is a readout of reduced Tor1 signaling. How Tor1 regulates BRG1 expression is not clear. Using a forward genetic screen for mutants that can sustain hyphal elongation in rich media, we found hog1, ssk2, and pbs2 mutants of the HOG mitogen-activated protein kinase pathway to express BRG1 irrespective of rapamycin. Furthermore, rapamycin lowers the basal activity of Hog1 through the functions of the two Hog1 tyrosine phosphatases Ptp2 and Ptp3. Active Hog1 represses the expression of BRG1 via the transcriptional repressor Sko1 as Sko1 disassociates from the promoter of BRG1 in the hog1 mutant or in rapamycin. Our data suggest that reduced Tor1 signaling lowers Hog1 basal activity via Hog1 phosphatases to activate BRG1 expression for hyphal elongation.