title: Post-transcriptional regulation of the yeast high affinity iron transport system.
abstract: Saccharomyces cerevisiae transcriptionally regulates the expression of the plasma membrane high affinity iron transport system in response to iron need. This transport system is comprised of the products of the FET3 and FTR1 genes. We show that Fet3p and Ftr1p are post-translationally regulated by iron. Incubation of cells in high iron leads to the internalization and degradation of both Fet3p and Ftr1p. Yeast strains defective in endocytosis (Deltaend4) show a reduced iron-induced loss of Fet3p-Ftr1p. In cells with a deletion in the vacuolar protease PEP4, high iron medium leads to the accumulation of Fet3p and Ftr1p in the vacuole. Iron-induced degradation of Fet3p-Ftr1p is significantly reduced in strains containing a deletion of a gene, VTA1, which is involved in multivesicular body (MVB) sorting in yeast. Sorting through the MVB can involve ubiquitination. We demonstrate that Ftr1p is ubiquitinated, whereas Fet3p is not ubiquitinated. Iron-induced internalization and degradation of Fet3p-Ftr1p occurs in a mutant strain of the E3 ubiquitin ligase RSP5 (rsp5-1), suggesting that Rsp5p is not required. Internalization of Fet3p-Ftr1p is specific for iron and requires both an active Fet3p and Ftr1p, indicating that it is the transport of iron through the iron permease Ftr1p that is responsible for the internalization and degradation of the Fet3p-Ftr1p complex.
authors.affiliation: Dipartimento di Scienze Microbiologiche Genetiche e Molecolari, Università di Messina, Salita Sperone 31, I-98166 Villaggio S. Agata, Messina I-98166, Italy.
authors.forename: M Rosa
authors.initials: MR
authors.lastname: Felice
authors.forename: Ivana
authors.initials: I
authors.lastname: De Domenico
authors.forename: Liangtao
authors.initials: L
authors.lastname: Li
authors.forename: Diane McVey
authors.initials: DM
authors.lastname: Ward
authors.forename: Beatrix
authors.initials: B
authors.lastname: Bartok
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musci
authors.forename: Jerry
authors.initials: J
authors.lastname: Kaplan
mesh_terms: D001692:Biological Transport; D015153:Blotting, Western; D002570:Ceruloplasmin / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D056827:Endosomal Sorting Complexes Required for Transport; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D007763:Lac Operon; D026901:Membrane Transport Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; C098723:FTR1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D003513:Cycloheximide; D007501:Iron; D002570:Ceruloplasmin; C085513:FET3 protein, S cerevisiae; D043743:Ubiquitin-Protein Ligase Complexes; D015719:Single-Strand Specific DNA and RNA Endonucleases; C469287:RSP5 protein, S cerevisiae