Huang Liping, Kirschke Catherine P, Gitschier Jane
Western Human Nutrition Research Center/Agriculture Research Service/United States Department of Agriculture and the Department of Nutrition and the Rowe Program in Genetics, University of California, Davis, California 95616, USA.
J Biol Chem. 2002 Jul 19;277(29):26389-95. doi: 10.1074/jbc.M200462200. Epub 2002 May 7.
We describe ZnT6, a new member of the CDF (cation diffusion facilitator) family of heavy metal transporters. The human ZNT6 gene was mapped at 2p21-22, while the mouse Znt6 was localized to chromosome 17. Overexpression of ZnT6 in both wild-type yeast and mutants that are deficient in cytoplasmic zinc causes growth inhibition, but this inhibition is abolished in mutant cells with high cytoplasmic zinc. ZnT6 may function in transporting the cytoplasmic zinc into the Golgi apparatus as well as the vesicular compartment, as evidenced by its overlapping intracellular localization with TGN38 and transferrin receptor in the normal rat kidney cells. We also demonstrate that the intracellular distributions of ZnT6 as well as ZnT4 are regulated by zinc in the normal rat kidney cells. The results from this report, combined with those from other studies, suggest that the intracellular zinc homeostasis is mediated by many ZnT proteins, which act in tissue-, cell-, and organelle-specific manners.
我们描述了锌转运体6(ZnT6),它是重金属转运蛋白CDF(阳离子扩散促进因子)家族的一个新成员。人类ZNT6基因定位于2p21 - 22,而小鼠Znt6定位于17号染色体。在野生型酵母和细胞质锌缺乏的突变体中过表达ZnT6都会导致生长抑制,但在细胞质锌含量高的突变细胞中这种抑制作用消失。ZnT6可能在将细胞质锌转运到高尔基体以及囊泡区室中发挥作用,这在正常大鼠肾细胞中其与TGN38和转铁蛋白受体的细胞内定位重叠得到了证明。我们还证明,在正常大鼠肾细胞中,ZnT6以及ZnT4的细胞内分布受锌的调节。本报告的结果与其他研究的结果相结合,表明细胞内锌稳态由许多ZnT蛋白介导,这些蛋白以组织、细胞和细胞器特异性的方式发挥作用。