Abstract
The baker's yeast Saccharomyces cerevisiae expresses three homologues of the Nramp family of metal transporters: Smf1p, Smf2p, and Smf3p, encoded by SMF1, SMF2, and SMF3, respectively. Here we report a comparative analysis of the yeast Smf proteins at the levels of localization, regulation, and function of the corresponding metal transporters. Smf1p and Smf2p function in cellular accumulation of manganese, and the two proteins are coregulated by manganese ions and the BSD2 gene product. Under manganese-replete conditions, Bsd2p facilitates trafficking of Smf1p and Smf2p to the vacuole, where these transport proteins are degraded. However, Smf1p and Smf2p localize to distinct cellular compartments under metal starvation: Smf1p accumulates at the cell surface, while Smf2p is restricted to intracellular vesicles. The third Nramp homologue, Smf3p, is quite distinctive. Smf3p is not regulated by Bsd2p or by manganese ions and is not degraded in the vacuole. Instead, Smf3p is down-regulated by iron through a mechanism that does not involve transcription or protein stability. Smf3p localizes to the vacuolar membrane independently of metal treatment, and yeast cells lacking Smf3p show symptoms of iron starvation. We propose that Smf3p helps to mobilize vacuolar stores of iron.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Blotting, Western
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Carrier Proteins / biosynthesis*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Cation Transport Proteins*
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Cell Membrane / chemistry
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Cell Membrane / metabolism
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Down-Regulation
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Fluorescent Antibody Technique, Indirect
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Gene Deletion
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Gene Expression Regulation, Fungal
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Intracellular Membranes / chemistry
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Intracellular Membranes / metabolism
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Iron-Binding Proteins*
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Manganese / metabolism
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Models, Biological
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Plasmids
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Protein Isoforms
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Protein Processing, Post-Translational
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Protein Structure, Secondary
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Time Factors
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Vacuoles / metabolism
Substances
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Carrier Proteins
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Cation Transport Proteins
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Iron-Binding Proteins
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Membrane Proteins
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Protein Isoforms
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SMF1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Smf2 protein, S cerevisiae
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Smf3 protein, S cerevisiae
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natural resistance-associated macrophage protein 1
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solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
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Manganese