Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation.
Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation.
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果蝇锌转运蛋白的功能研究揭示了膳食锌吸收和调节的机制
DOI：
10.1186/1741-7007-11-101
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发表时间：
2013-09-24
期刊：
影响因子：
5.4
通讯作者：
Zhou B
中科院分区：
文献类型：
--
作者：
Qin Q;Wang X;Zhou B
背景：锌是许多蛋白质功能的关键，但饮食中锌的吸收过程尚不清楚。目前关于膳食锌吸收的知识是零散的，并且大部分来自不完整的哺乳动物研究。为了全面了解这一过程，我们系统地描述了所有锌转运蛋白（即 Zip 和 ZnT 家族成员）在遗传上顺从的模式生物（果蝇）中在膳食锌吸收中可能发挥的作用。结果：一组质膜驻留锌转运蛋白被确定负责将锌从内腔吸收到肠细胞中，然后将锌排出到循环系统中。 dZip1 和 dZip2 是两个功能重叠的锌输入蛋白，负责将锌从管腔吸收到肠上皮细胞中。锌进入循环系统是通过另外两个功能重叠的锌输出蛋白 dZnT1 及其同源物 CG5130 (dZnT77C) 介导的。令人有些惊讶的是，细胞内 ZnT 蛋白的阵列，包括高尔基体驻留的 dZnT7，似乎并不直接参与膳食锌的吸收。通过调节身体不同部位的锌状态，我们发现，与铁的吸收相比，膳食锌吸收的调节对身体需求或肠道外的锌状态没有反应。参与膳食锌吸收的锌转运蛋白，包括输入端 dZip1 和 dZip2 以及输出端 dZnT1，分别在 RNA 和蛋白质水平上受到肠上皮细胞中锌的调节。结论：我们使用模式生物果蝇的研究由此开始揭示膳食锌吸收及其调节控制的全面概况，这一过程在哺乳动物生物体中仍不完全了解。所获得的知识将为未来的哺乳动物研究提供参考，并能够从进化的角度理解这一重要过程。
Background:Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster.Results:A set of plasma membrane-resident zinc transporters was identified to be responsible for absorbing zinc from the lumen into the enterocyte and the subsequent exit of zinc to the circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Exit of zinc to the circulation is mediated through another two functionally overlapping zinc exporters, dZnT1, and its homolog CG5130 (dZnT77C). Somewhat surprisingly, it appears that the array of intracellular ZnT proteins, including the Golgi-resident dZnT7, is not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that regulation of dietary zinc absorption, in contrast to that of iron, is unresponsive to bodily needs or zinc status outside the gut. The zinc transporters that are involved in dietary zinc absorption, including the importers dZip1 and dZip2, and the exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte.Conclusions:Our study using the model organism Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulatory control, a process that is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies, and also enable an appreciation of this important process from an evolutionary perspective.
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