TY - JOUR
T1 - Negative control of heavy metal uptake by the Saccharomyces cerevisiae BSD2 gene
AU - Liu, Xiu Fen
AU - Supek, Frantisek
AU - Nelson, Nathan
AU - Culotta, Valeria Cizewski
PY - 1997/5/2
Y1 - 1997/5/2
N2 - We have previously shown that mutations in the Saccharomyces cerevisiae BSD2 gene suppress oxidative damage in cells lacking superoxide dismutase and also lead to hyperaccumulation of copper ions. We demonstrate here that bsd2 mutant cells additionally accumulate high levels of cadmium and cobalt. By biochemical fractionation and immunofluorescence microscopy, BSD2 exhibited localization to the endoplasmic reticulum, suggesting that BSD2 acts a t a distance to inhibit metal uptake from the growth medium. This BSD2 control of ion transport occurs independently of the CTR1 and FET4 metal transport systems. Genetic suppressor analysis revealed that hyperaccumulation of copper and cadmium in bsd2 mutants is mediated through SMF1, previously shown to encode a plasma membrane trans porter for manganese. A nonsense mutation removing the carboxyl-terminal hydrophobic domain of SMF1 was found to mimic a smf1 gene deletion by eliminating the copper and cadmium toxicity of bsd2 mutants and also by precluding the bsd2 suppression of superoxide dismutase deficiency. However, inactivation of SMF1 did not eliminate the elevated cobalt levels in bsd2 mutants. Instead, this cobalt accumulation was found to be specifically mediated through the SMF1 homologue, SMF2. Hence, BSD2 prevents metal hyperaccumulation by exerting negative control over the SMF1 and SMF2 metal transport systems.
AB - We have previously shown that mutations in the Saccharomyces cerevisiae BSD2 gene suppress oxidative damage in cells lacking superoxide dismutase and also lead to hyperaccumulation of copper ions. We demonstrate here that bsd2 mutant cells additionally accumulate high levels of cadmium and cobalt. By biochemical fractionation and immunofluorescence microscopy, BSD2 exhibited localization to the endoplasmic reticulum, suggesting that BSD2 acts a t a distance to inhibit metal uptake from the growth medium. This BSD2 control of ion transport occurs independently of the CTR1 and FET4 metal transport systems. Genetic suppressor analysis revealed that hyperaccumulation of copper and cadmium in bsd2 mutants is mediated through SMF1, previously shown to encode a plasma membrane trans porter for manganese. A nonsense mutation removing the carboxyl-terminal hydrophobic domain of SMF1 was found to mimic a smf1 gene deletion by eliminating the copper and cadmium toxicity of bsd2 mutants and also by precluding the bsd2 suppression of superoxide dismutase deficiency. However, inactivation of SMF1 did not eliminate the elevated cobalt levels in bsd2 mutants. Instead, this cobalt accumulation was found to be specifically mediated through the SMF1 homologue, SMF2. Hence, BSD2 prevents metal hyperaccumulation by exerting negative control over the SMF1 and SMF2 metal transport systems.
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U2 - 10.1074/jbc.272.18.11763
DO - 10.1074/jbc.272.18.11763
M3 - Article
C2 - 9115231
AN - SCOPUS:0001726322
SN - 0021-9258
VL - 272
SP - 11763
EP - 11769
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 18
ER -