title: Post-translation control of Nramp metal transport in yeast. Role of metal ions and the BSD2 gene.
abstract: The Saccharomyces cerevisiae SMF1 gene encodes a member of the well conserved family of Nramp metal transport proteins. Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. cerevisiae BSD2 gene. We now demonstrate that this regulation occurs at the level of protein stability. In wild type strains, the bulk of Smf1p is normally directed to the vacuole and is rapidly degraded by vacuolar proteases in a PEP4-dependent manner. In bsd2Delta mutants, Smf1p fails to enter the vacuole, and the Nramp protein is stabilized. Metal ions themselves play an important role in the post-translational regulation of Smf1p. The depletion of heavy metals from the growth medium effects stabilization of Smf1p and additionally results in accumulation of this transporter at the cell surface. Supplementation of manganese alone is sufficient to trigger rapid degradation of Smf1p in a Bsd2p-dependent manner. Together the action of Bsd2p and metal ions provide a rapid and effective means for controlling Nramp metal transport in response to environmental changes.
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University, School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: X F
authors.initials: XF
authors.lastname: Liu
authors.forename: V C
authors.initials: VC
authors.lastname: Culotta
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D005800:Genes, Fungal; D006868:Hydrolysis; D017136:Ion Transport; D033862:Iron-Binding Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013347:Subcellular Fractions / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2