title: Substrate-mediated remodeling of methionine transport by multiple ubiquitin-dependent mechanisms in yeast cells.
abstract: Plasma membrane transport of single amino-acid methionine in yeast is shown to be mediated by at least seven different permeases whose activities are transcriptionaly and post-transcriptionaly regulated by different ubiquitin-dependent mechanisms. Upon high extracellular methionine exposure, three methionine-permease genes are repressed while four others are induced. SCF(Met30), SCF(Grr1) and Rsp5 ubiquitin ligases are the key actors of the ubiquitin-dependent remodeling of methionine transport. In addition to regulating the activity of Met4, the SCF(Met30) ubiquitin ligase is shown to convey an intracellular signal to a membrane initiated signaling pathway by controlling the nuclear concentration of the Stp1 transcription factor. By coupling intra- and extracellular metabolite sensing, SCF(Met30) thus allows yeast cells to accurately adjust the intermediary sulfur metabolism to the growth conditions. The multiple ubiquitin-dependent mechanisms that function in methionine transport regulation further exemplify the pervasive role of ubiquitin in the adaptation of single-cell organisms to environmental modifications.
authors.affiliation: Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, Gif-sur-Yvettte, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Menant
authors.forename: Régine
authors.initials: R
authors.lastname: Barbey
authors.forename: Dominique
authors.initials: D
authors.lastname: Thomas
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D004795:Enzyme Stability; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D008715:Methionine / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D013457:Sulfur Compounds / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: D026905:Amino Acid Transport Systems; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C073675:MET4 protein, S cerevisiae; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C074632:STP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C421606:Stp2 protein, S cerevisiae; D013457:Sulfur Compounds; D015534:Trans-Activators; D014157:Transcription Factors; D025801:Ubiquitin; C035737:major urinary proteins; D008715:Methionine; D043743:Ubiquitin-Protein Ligase Complexes; D044843:SKP Cullin F-Box Protein Ligases; C469287:RSP5 protein, S cerevisiae