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Mercury and cadmium trigger expression of the copper importer Ctr1B, which enables Drosophila to thrive on heavy metal-loaded food

Balamurugan, Kuppusamy ; Hua, Haiqing ; Georgiev, Oleg ; Schaffner, Walter

In: Biological Chemistry, 2009, vol. 390, no. 2, p. 109-113

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    Titel
    • Mercury and cadmium trigger expression of the copper importer Ctr1B, which enables Drosophila to thrive on heavy metal-loaded food
    Autor
    • Balamurugan, Kuppusamy. Institute of Molecular Biology, University of Zurich, Winterthurer Str. 190, CH-8057 Zurich, Switzerland
    • Hua, Haiqing. Institute of Molecular Biology, University of Zurich, Winterthurer Str. 190, CH-8057 Zurich, Switzerland
    • Georgiev, Oleg. Institute of Molecular Biology, University of Zurich, Winterthurer Str. 190, CH-8057 Zurich, Switzerland
    • Schaffner, Walter. Institute of Molecular Biology, University of Zurich, Winterthurer Str. 190, CH-8057 Zurich, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Biological Chemistry, 2009, vol. 390, no. 2, p. 109-113. Walter de Gruyter
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:301149
    Summary
    Organisms from insects to mammals respond to heavy metal load (copper, zinc, cadmium, and mercury) by activating the metal-responsive transcription factor 1 (MTF-1). MTF-1 binds to short DNA sequence motifs, termed metal response elements, and boosts transcription of a number of genes, notably those for metallothioneins. In Drosophila, MTF-1 somewhat counter-intuitively also activates transcription of a copper importer gene (Ctr1B) in response to copper starvation. Here, we report that mutant flies lacking Ctr1B are extremely sensitive to cadmium and mercury treatment, but can be rescued by excess copper in the food. We thus propose that copper, by competing for binding sites on cellular proteins, alleviates the toxic effects of mercury and cadmium. Such a scenario also explains a seemingly fortuitous metal response, namely, that cadmium and mercury strongly induce the expression of a Ctr1B reporter gene. Thus, the transcription enhancer/promoter region of the Ctr1B copper importer gene is subject to three modes of regulation. All of them depend on MTF-1 and all make biological sense, namely, (i) induction by copper starvation, (ii) repression by copper abundance, and (iii), as shown here, induction by cadmium or mercury at normal copper supply