The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice
The acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice
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DOI：
10.1074/jbc.m305000200
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发表时间：
2003-08-29
影响因子：
4.8
通讯作者：
Andrews, GK
中科院分区：
文献类型：
--
作者：
Dufner-Beattie, J;Wang, FD;Andrews, GK
人类ZIP4基因(SLC39A4)是肠性肢端皮炎锌代谢异常的候选基因。为了了解它在锌稳态中的作用，我们研究了小鼠ZIP4的功能和表达。该基因编码一种保守的八跨膜蛋白，可以特异性地增加锌进入转基因细胞的内流。该基因在肠道和胚胎内脏卵黄囊等参与营养吸收的组织中表达旺盛，并受锌的动态调节。膳食缺锌导致这些组织中ZIP4mRNA的积累显著增加，而注射锌或增加膳食中的锌含量会迅速降低其丰度。锌还可调节ZIP4蛋白在肠上皮细胞和内脏内胚层细胞顶面的积聚。这些结果提供了令人信服的证据，证明ZIP4是一种锌转运蛋白，在锌稳态中发挥重要作用，而锌稳态是人类肠病肢端皮炎的缺陷过程。
The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. These results provide compelling evidence that ZIP4 is a zinc transporter that plays an important role in zinc homeostasis, a process that is defective in acrodermatitis enteropathica in humans.