Copper homeostasis in Drosophila by complex interplay of import, storage and behavioral avoidance
Copper homeostasis in Drosophila by complex interplay of import, storage and behavioral avoidance
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DOI：
10.1038/sj.emboj.7601543
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发表时间：
2007-02-21
期刊：
影响因子：
11.4
通讯作者：
Schaffner, Walter
中科院分区：
文献类型：
--
作者：
Balamurugan, Kuppusamy;Egli, Dieter;Schaffner, Walter
铜是一种必需的但具有潜在毒性的微量元素。在果蝇中，金属应答转录因子（MTF-1）在铜稳态中起着双重作用：在有限的铜浓度下，它诱导Ctr 1B铜输入基因，而在高铜浓度下，它主要诱导金属硫蛋白基因。在这里，我们发现，尽管Ctr 1B基因在高铜浓度下下调，但该蛋白质在肠细胞的质膜上持续数小时，从而填充细胞内的铜储存。果蝇可能会冒着过度积累铜的风险，以克服一段时间的铜短缺。事实上，我们发现富含铜的果蝇为它们的后代提供了重要的供应，使下一代能够在低铜食物中茁壮成长。我们还描述了两种额外的铜处理模式：行为避免含有高（>= 0.5mM）铜水平的食物，以及DmATP 7（Wilson/Menkes病铜输出者的果蝇同源物）抵消铜毒性的能力。受管制的进口、储存、出口和避免高铜食物在可变的环境条件下建立了足够的铜稳态。
Copper is an essential but potentially toxic trace element. In Drosophila, the metal-responsive transcription factor (MTF-1) plays a dual role in copper homeostasis: at limiting copper concentrations, it induces the Ctr1B copper importer gene, whereas at high copper concentrations, it mainly induces the metallothionein genes. Here we find that, despite the downregulation of the Ctr1B gene at high copper concentrations, the protein persists on the plasma membrane of intestinal cells for many hours and thereby fills the intracellular copper stores. Drosophila may risk excessive copper accumulation for the potential benefit of overcoming a period of copper scarcity. Indeed, we find that copper-enriched flies donate a vital supply to their offspring, allowing the following generation to thrive on low-copper food. We also describe two additional modes of copper handling: behavioral avoidance of food containing high (>= 0.5mM) copper levels, as well as the ability of DmATP7, the Drosophila homolog of Wilson/Menkes disease copper exporters, to counteract copper toxicity. Regulated import, storage, export, and avoidance of high-copper food establish an adequate copper homeostasis under variable environmental conditions.