Post-translation control of Nramp metal transport in yeast - Role of metalions and the BSD2 gene

The Saccharomyces cerevisiae SMF1 gene encodes a member of the well conserv ed family of Nramp metal transport proteins. Previously, we determined that heavy metal uptake by Smf1p was down-regulated by the product of the S. ce revisiae BSD2 gene. We now demonstrate that this regulation occurs at the l evel of protein stability. In wild type strains, the bulk of Smf1p is norma lly directed to the vacuole and is rapidly degraded by vacuolar proteases i n a PEP4-dependent manner. In bsd2 Delta 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 depletio n of heavy metals from the growth medium effects stabilization of Smf1p and additionally results in accumulation of this transporter at the cell surfa ce. Supplementation of manganese alone is sufficient to trigger rapid degra dation of Smf1p in a Bsd2p-dependent manner. Together the action of Bsd2p a nd metal ions provide a rapid and effective means for controlling Nramp met al transport in response to environmental changes.