Distinct Ire1-driven transcriptional responses control morphogenesis in Candida albicans
The ability of pathogenic yeast Candida albicans to cause infections in humans depends on morphogenesis, the ability to switch from a spherical yeast to a filamentous hyphal form. Morphogenesis in C. albicans requires Ire1, a transmembrane protein responsible for binding misfolded proteins and initiating the Unfolded Protein Response (UPR). The UPR is a signaling pathway activated in response to the accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER). Ire1 activation in the ER membrane leads to splicing of cytosolic HAC1 mRNA and subsequent UPR target gene upregulation by transcription factor Hac1. In C. albicans, the specific UPR target genes required for morphogenesis are unknown. We utilized RNA-Sequencing to assess the transcriptome of UPR-deficient cells in misfolded protein- and morphogenesis-inducing conditions. Surprisingly, we found little overlap between the datasets, suggesting that a specific Ire1 transcriptional signature drives filamentous growth. Moreover, Hac1 is only partially required for morphogenesis, suggesting a role of Hac1-independent Ire1 function in filamentation. We propose that the cell wall stress response and regulated Ire1-dependent decay (RIDD) are potential Hac1-independent mechanisms connecting Ire1 to morphogenesis in C. albicans. Overall design: To characterize the UPR in C. albicans and its role in morphogenesis, we used a control strain (DAY286) and a strain with dimished expression of UPR activator Ire1 (ire1DX). Strains were grown with the proteotoxic stressor tunicamycin at 30°C for two hours and with morphogenesis-inducing fetal bovine serum at 37°C for four hours. Control samples were untreated and grown at 30°C for two hours. Each condition was performed in triplicate.