title: Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae.
abstract: All cells regulate their intracellular zinc levels. In yeast, zinc uptake is mediated by Zrt1p and Zrt2p, which belong to the ZIP family of metal transporters. Under zinc limitation, ZRT1 and ZRT2 transcription is induced by the Zap1p transcriptional activator. We describe here a new component of zinc homeostasis, vacuolar zinc storage, that is also regulated by Zap1p. Zinc-replete cells accumulate zinc in the vacuole via the Zrc1p and Cot1p transporters. Our results indicate that another zinc transporter, Zrt3p, mobilizes this stored zinc in zinc-limited cells. ZRT3 is a Zap1p-regulated gene whose transcription increases in low zinc. Zrt3p is also a member of the ZIP family and it localizes to the vacuolar membrane. The effects of ZRT3 mutation and overexpression on cell growth, cellular zinc accumulation and intracellular labile zinc pools are all consistent with its proposed role. Furthermore, we demonstrate that zrt3 mutants inefficiently mobilize stored zinc to offset deficiency. Thus, our studies define a system of zinc influx and efflux transporters in the vacuole that play important roles in zinc homeostasis.
authors.affiliation: Department of Nutritional Sciences, 217 Gwynn Hall, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: MacDiarmid
authors.forename: L A
authors.initials: LA
authors.lastname: Gaither
authors.forename: D
authors.initials: D
authors.lastname: Eide
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006706:Homeostasis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D012441:Saccharomyces cerevisiae / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: C076223:COT1 protein, S cerevisiae; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C088843:ZRC1 protein, S cerevisiae; C098750:ZRT1 protein, S cerevisiae; C101759:ZRT2 protein, S cerevisiae; C411567:Zrt3 protein, S cerevisiae; D015032:Zinc