title: The activity of RTA2, a downstream effector of the calcineurin pathway, is required during tunicamycin-induced ER stress response in Candida albicans.
abstract: 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.
authors.affiliation: Yeast Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Edwina
authors.initials: E
authors.lastname: Thomas
authors.affiliation: Yeast Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Sircaik
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Roman
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Laboratory of Integrative Structural & Chemical Biology, UMR CNRS F-7258, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Brunel
authors.affiliation: Yeast Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India.
authors.forename: Atul K
authors.initials: AK
authors.lastname: Johri
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pla
authors.affiliation: Yeast Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi-110067, India sneh@mail.jnu.ac.in.
authors.forename: Sneh L
authors.initials: SL
authors.lastname: Panwar
mesh_terms: D000890:Anti-Infective Agents / Q000633:toxicity*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D014415:Tunicamycin / Q000633:toxicity*; D056811:Unfolded Protein Response
chemical_list: D000890:Anti-Infective Agents; D005656:Fungal Proteins; D014415:Tunicamycin
keywords: Candida albicans; ER stress; Hac1; RTA2; calcineurin; unfolded protein response