title: The bZIP transcription factor Rca1p is a central regulator of a novel CO₂ sensing pathway in yeast.
abstract: Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO(2) concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO(2) and identify the bZIP transcription factor Rca1p as the first CO(2) regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO(2) build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO(2) sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO(2) availability in environments as diverse as the phagosome, yeast communities or liquid culture.
authors.affiliation: School of Biosciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Fabien
authors.initials: F
authors.lastname: Cottier
authors.forename: Martine
authors.initials: M
authors.lastname: Raymond
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.forename: Marianne
authors.initials: M
authors.lastname: Bolstad
authors.forename: Worraanong
authors.initials: W
authors.lastname: Leewattanapasuk
authors.forename: Claudia
authors.initials: C
authors.lastname: Jiménez-López
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lorenz
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.forename: Libuše
authors.initials: L
authors.lastname: Váchová
authors.forename: Norman
authors.initials: N
authors.lastname: Pavelka
authors.forename: Zdena
authors.initials: Z
authors.lastname: Palková
authors.forename: Fritz A
authors.initials: FA
authors.lastname: Mühlschlegel
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D058448:Biota; D002245:Carbon Dioxide / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004777:Environment; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008828:Microbiological Techniques; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D030781:Organisms, Genetically Modified; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism; D053038:Quorum Sensing / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015003:Yeasts / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; D002245:Carbon Dioxide; D008666:Metalloendopeptidases; D000251:Adenosine Triphosphatases; C102166:YTA12 protein, S cerevisiae