title: Vesicular Trafficking Systems Impact TORC1-Controlled Transcriptional Programs in Saccharomyces cerevisiae.
abstract: The Target of Rapamycin Complex I (TORC1) orchestrates global reprogramming of transcriptional programs in response to myriad environmental conditions, yet, despite the commonality of the TORC1 complex components, different TORC1-inhibitory conditions do not elicit a uniform transcriptional response. In Saccharomyces cerevisiae, TORC1 regulates the expression of nitrogen catabolite repressed (NCR) genes by controlling the nuclear translocation of the NCR transactivator Gln3. Moreover, Golgi-to-endosome trafficking was shown to be required for nuclear translocation of Gln3 upon a shift from rich medium to the poor nitrogen source proline, but not upon rapamycin treatment. Here, we employed microarray profiling to survey the full impact of the vesicular trafficking system on yeast TORC1-orchestrated transcriptional programs. In addition to the NCR genes, we found that ribosomal protein, ribosome biogenesis, phosphate-responsive, and sulfur-containing amino acid metabolism genes are perturbed by disruption of Golgi-to-endosome trafficking following a nutritional shift from rich to poor nitrogen source medium, but not upon rapamycin treatment. Similar to Gln3, defects in Golgi-to-endosome trafficking significantly delayed cytoplasmic-nuclear translocation of Sfp1, but did not detectably affect the cytoplasmic-nuclear or nuclear-cytoplasmic translocation of Met4, which are the transactivators of these genes. Thus, Golgi-to-endosome trafficking defects perturb TORC1 transcriptional programs via multiple mechanisms. Our findings further delineate the downstream transcriptional responses of TORC1 inhibition by rapamycin compared with a nitrogen quality downshift. Given the conservation of both TORC1 and endomembrane networks throughout eukaryotes, our findings may also have implications for TORC1-mediated responses to nutritional cues in mammals and other eukaryotes.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Kingsbury
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 carde004@mc.duke.edu.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cardenas
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001692:Biological Transport; D011992:Endosomes / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006056:Golgi Apparatus / Q000378:metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014158:Transcription, Genetic; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Golgi-to-endosome trafficking; phosphate-responsive network; rapamycin mechanism of action; ribosome biogenesis genes; sulfur-containing amino acid metabolism genes