The activity ofRTA2,a downstream effector of the calcineurin pathway, is required during tunicamycin-induced ER stress response inCandida albicans
| Autor: | Jean Michel Brunel, Sneh Lata Panwar, Jesús Pla, Shabnam Sircaik, Atul Kumar Johri, Edwina Thomas, Elvira Román |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Fungal protein
Calcineurin Pathway Effector Tunicamycin General Medicine Biology Endoplasmic Reticulum Stress biology.organism_classification Applied Microbiology and Biotechnology Microbiology Cell biology Fungal Proteins Calcineurin chemistry.chemical_compound Anti-Infective Agents chemistry Candida albicans Unfolded Protein Response Unfolded protein response Transcription factor Gene Deletion |
| Zdroj: | FEMS Yeast Research. :fov095 |
| ISSN: | 1567-1364 |
| DOI: | 10.1093/femsyr/fov095 |
| Popis: | In this study, we demonstrate a novel function of a downstream effector molecule of the calcineurin pathway, RTA2 (Resistance To Aminocholesterol), in ER stress response. The deletion of RTA2 increases susceptibility to the ER stressor tunicamycin and morpholine-like drug, 7-aminocholesterol. Additionally, the expression of RTA2 is also transcriptionally induced by ergosterol biosynthesis inhibitors and cell-wall-damaging agents. As tunicamycin induces the unfolded protein response pathway (UPR) via the transcription factor, HAC1, we monitored the expression of a subset of HAC1-dependent UPR target genes in rta2Δ/Δ cells. Upon tunicamycin exposure, rta2Δ/Δ cells displayed a significantly reduced expression of UPR genes, in spite of only a moderate decrease in the HAC1 spliced mRNA levels and no change in Hac1 protein levels. Furthermore, hac1Δ/Δrta2Δ/Δ cells display an exacerbated sensitivity to tunicamycin compared to the single mutants. We propose that functional RTA2 is requisite for the regulation of Hac1p-dependent UPR target genes to maximal levels, thereby assisting survival during ER stress. Collectively, this study proposes, for the first time, existence of an interplay between the Hac1p- and calcineurin- controlled networks via a downstream effector molecule of the latter, RTA2, to facilitate survival during ER stress in Candida albicans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|