title: Yeast nitrogen catabolite repression is sustained by signals distinct from glutamine and glutamate reservoirs.
abstract: Nitrogen catabolite repression (NCR) is a wide transcriptional regulation program enabling baker's yeast to downregulate genes involved in the utilization of poor nitrogen sources when preferred ones are available. Nowadays, glutamine and glutamate, the major nitrogen donors for biosyntheses, are assumed to be key metabolic signals regulating NCR. NCR is controlled by the conserved TORC1 complex, which integrates nitrogen signals among others to regulate cell growth. However, accumulating evidence indicate that the TORC1-mediated control of NCR is only partial, arguing for the existence of supplementary regulatory processes to be discovered. In this work, we developed a genetic screen to search for new players involved in NCR signaling. Our data reveal that the NADP-glutamate dehydrogenase activity of Gdh1 negatively regulates NCR-sensitive gene transcription. By determining the total, cytoplasmic and vacuolar pools of amino acids, we show that there is no positive correlation between glutamine/glutamate reservoirs and the extent of NCR. While our data indicate that glutamine could serve as initial trigger of NCR, they show that it is not a sufficient signal to sustain repression and point to the existence of yet unknown signals. Providing additional evidence uncoupling TORC1 activity and NCR, our work revisits the dogmas underlying NCR regulation.
authors.affiliation: Institut de Recherches Microbiologiques J.-M. Wiame, 1070, Brussels, Belgium.|Laboratoire de Biologie du Transport Membranaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fayyad-Kazan
authors.affiliation: Institut de Recherches Microbiologiques J.-M. Wiame, 1070, Brussels, Belgium.|Laboratoire de Microbiologie, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Feller
authors.affiliation: Unité de Biotechnologie, 1070, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Bodo
authors.affiliation: Laboratoire de Biologie du Transport Membranaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Boeckstaens
authors.affiliation: Laboratoire de Biologie du Transport Membranaire, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: A M
authors.initials: AM
authors.lastname: Marini
authors.affiliation: Institut de Recherches Microbiologiques J.-M. Wiame, 1070, Brussels, Belgium.|Laboratoire de Microbiologie, Institut de Biologie et de Médecine Moléculaires, Université Libre de Bruxelles, 6041, Gosselies, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Dubois
authors.affiliation: Institut de Recherches Microbiologiques J.-M. Wiame, 1070, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Georis
mesh_terms: D015966:Gene Expression Regulation, Fungal; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D005973:Glutamine; D018698:Glutamic Acid; D009584:Nitrogen