Boch, A; Trampczynska, A; Simm, C; Taudte, N; Krämer, U; Clemens, S: Loss of Zhf and the tightly regulated Zn uptake system SpZrt1 in Schizosaccharomyces pombe reveals the delicacy of cellular Zn balance., FEMS Yeast Research, 8, 883-896 (2008), doi:10.1111/j.1567-1364.2008.00414.x
Abstract:
Zn is an essential micronutrient yet can be toxic when present in excess. Zn acquisition and distribution are dependent on tightly controlled transport of Zn2+ ions. Schizosaccharomyces pombe represents a second eukaryotic model to study cellular metal homeostasis. In several ways its micronutrient metabolism is fundamentally different from Saccharomyces cerevisiae. We identified the first Zn2+ uptake system in S. pombe and named it SpZrt1. Knock-out strains for all three ZIP transporters in fission yeast were constructed. Only zrt1 cells were unable to grow at low Zn2+ and showed reduced 65Zn2+ uptake. Elemental profiles revealed a strong decrease in Zn accumulation. Cd2+ ions inhibited uptake but not Fe2+ or Mn2+. Both mRNA abundance and protein amount are tightly regulated. Zrt1 activity is rapidly shut down upon transfer of Zn-deficient cells to Zn-replete conditions. In cells lacking Zhf, a transporter mediating ER storage of Zn, this response is about 100fold more sensitive. Thus, removal of excess of Zn from the cytosol is largely Zhf-dependent. Moreover, cells deficient for both transporters are no longer able to adjust to changing external Zn2+ concentrations. Optimal growth is restricted to a narrow range of Zn2+ concentrations illustrating the fine balance between micronutrient deficiency and toxicity.
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