Saccharomyces cerevisiae expresses three functionally distinct homologues of the Nramp family of metal transporters

The baker's yeast Saccharomyces cerevisiae expresses three homologues of th e Nramp family of metal transporters: Smf1p, Smf2p, and Smf3p, encoded by S MF1, SMF2, and SMF3, respectively. Here we report a comparative analysis of the yeast Smf proteins at the levels of localization, regulation, and func tion of the corresponding metal transporters. Smf1p and Smf2p function in c ellular accumulation of manganese, and the two proteins are coregulated by manganese ions and the BSD2 gene product. Under manganese-replete condition s, Bsd2p facilitates trafficking of Smf1p and Smf2p to the vacuole, where t hese 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 membran e independently of metal treatment, and yeast cells lacking Smf3p show symp toms of iron starvation. We propose that Smf3p helps to mobilize vacuolar s tores of iron.