Southon Adam, Farlow Ashley, Norgate Melanie, Burke Richard, Camakaris James
Department of Genetics, The University of Melbourne, Victoria 3010, Australia.
J Exp Biol. 2008 Mar;211(Pt 5):709-16. doi: 10.1242/jeb.014159.
Divalent metal ion transporter 1 (DMT1; also known as SLC11A2) can transport several metals including Fe and Cu in mammalian systems. We set out to determine whether Malvolio (Mvl), the Drosophila melanogaster orthologue of DMT1, can also transport Cu. Overexpression of Mvl caused Cu accumulation in Drosophila S2 cultured cells and conversely dsRNAi knockdown of endogenous Mvl reduced cellular Cu levels. Cell viability under Cu limiting conditions was reduced following dsRNAi knockdown. A homozygous viable Mvl loss-of-function mutant (Mvl(97f)) was sensitive to excess Cu and female Mvl(97f) flies were also sensitive to Cu limitation. An MtnA-EYFP reporter was used as a proxy measure of Cu distribution within Mvl(97f/+) larvae. Under basal conditions Cu levels were reduced in the anterior midgut and proventriculus relative to control larvae. These results demonstrate Mvl is a functional Cu transporter and that despite partial functional redundancy with the Ctr1 proteins, Cu uptake through this pathway is necessary for optimal viability at the cellular and organismal levels.
二价金属离子转运蛋白1(DMT1;也称为SLC11A2)在哺乳动物系统中可以转运包括铁和铜在内的多种金属。我们着手确定果蝇中DMT1的同源物马尔沃利奥(Mvl)是否也能转运铜。Mvl的过表达导致果蝇S2培养细胞中铜积累,相反,内源性Mvl的dsRNA干扰敲低降低了细胞内铜水平。dsRNA干扰敲低后,在铜限制条件下细胞活力降低。一个纯合可行的Mvl功能丧失突变体(Mvl(97f))对过量铜敏感,雌性Mvl(97f)果蝇对铜限制也敏感。使用MtnA-EYFP报告基因作为Mvl(97f/+)幼虫体内铜分布的替代测量指标。在基础条件下,相对于对照幼虫,前中肠和前胃中的铜水平降低。这些结果表明Mvl是一种功能性铜转运蛋白,并且尽管与Ctr1蛋白存在部分功能冗余,但通过该途径的铜摄取对于细胞和生物体水平的最佳活力是必要的。