Compartmentalized zinc deficiency and toxicities caused by ZnT and Zip gene over expression result in specific phenotypes in Drosophila
Compartmentalized zinc deficiency and toxicities caused by ZnT and Zip gene over expression result in specific phenotypes in Drosophila
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DOI：
10.1016/j.biocel.2014.12.017
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发表时间：
2015-03-01
影响因子：
4
通讯作者：
Burke, Richard
中科院分区：
文献类型：
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作者：
Dechen, Kesang;Richards, Christopher D.;Burke, Richard
锌离子跨细胞膜的运动主要通过编码多跨膜结构域蛋白的两个锌转运基因家族来实现。 Zip 家族的成员通常将锌从细胞外或从亚细胞器的内腔（例如内质网、高尔基体、核内体或储存液泡）转运到细胞质中。 ZnT 蛋白使锌向相反方向移动，导致锌从细胞流出或摄取到细胞器中。细胞和全身水平上的锌稳态是通过众多 Zip 和 ZnT 蛋白的协调作用实现的，哺乳动物中有 24 种，黑腹醋蝇中有 17 种。此前，我们已经确定了果蝇眼中的锌毒性表型，该表型是由 dZip42C.1 (dZip1) 的靶向过度表达结合 dZnT63C (dZnT1) 的敲低引起的。一般来说，这种表型可以通过增加锌流出或减少吸收来挽救，并通过减少流出或增加吸收而加剧。现在我们已经鉴定出另外三种由 dZnT86D、dZnT86D(eGFP) 和 dZip71B(FLAG) 过度表达引起的锌稳态表型。遗传和饮食控制实验表明，这三种表型彼此不同，也与我们最初的锌毒性表型不同。基于这些数据和每种锌转运蛋白的大致亚细胞定位，我们提出每种表型代表这些细胞内锌的不同重新分布，分别导致高尔基体锌毒性、高尔基体锌缺乏和高尔基体/其他细胞器锌联合毒性。我们能够根据剩余的果蝇 Zip 和 ZnT 基因与三种新的锌动态平衡表型的相互作用将它们分为几个功能类别，从而可以更详细地定义每种锌转运蛋白的作用。这项研究强调了锌的重新分布在特定组织内可能产生的不同影响，并确定高尔基体对锌过量和不足特别敏感。 (C) 2015 Elsevier Ltd. 保留所有权利。
Movement of zinc ions across cellular membranes is achieved mainly by two families of zinc transport genes encoding multi-transmembrane domain proteins. Members of the Zip family generally transport zinc into the cytosol, either from outside the cell or from the lumen of subcellular organelles such as the endoplasmic reticulum, Golgi, endosomes or storage vacuoles. ZnT proteins move zinc in the opposite direction, resulting in efflux from the cell or uptake into organelles. Zinc homeostasis at both the cellular and systemic level is achieved by the coordinated action of numerous Zip and ZnT proteins, twenty-four in mammals and seventeen in the vinegar fly Drosophila melanogaster. Previously, we have identified a zinc toxicity phenotype in the Drosophila eye, caused by targeted over expression of dZip42C.1 (dZip1) combined with knockdown of dZnT63C (dZnT1). In general, this phenotype was rescued by increased zinc efflux or decreased uptake and was exacerbated by decreased efflux or increased uptake. Now we have identified three additional zinc dyshomeostasis phenotypes caused by over expression of dZnT86D, dZnT86D(eGFP) and dZip71B(FLAG). Genetic and dietary manipulation experiments showed that these three phenotypes all differ both from each other and from our original zinc toxicity phenotype. Based on these data and the approximate subcellular localization of each zinc transport protein, we propose that each phenotype represents a different redistribution of zinc within these cells, resulting in a Golgi zinc toxicity, a Golgi zinc deficiency and a combined Golgi/other organelle zinc toxicity respectively. We are able to group the remaining Drosophila Zip and ZnT genes into several functional categories based on their interaction with the three novel zinc dyshomeostasis phenotypes, allowing the role of each zinc transport protein to be defined in greater detail. This research highlights the differential effects that redistribution of zinc can have within a particular tissue and identifies the Golgi as being particularly sensitive to both excess and insufficient zinc. (C) 2015 Elsevier Ltd. All rights reserved.