A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane
A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane
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DOI：
10.1074/jbc.m200577200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Ford, D
中科院分区：
文献类型：
--
作者：
Cragg, RA;Christie, GR;Ford, D
锌是一个广泛的细胞过程中必不可少的，因此，它是重要的，以阐明锌稳态的分子机制。到目前为止，没有锌转运蛋白表达的肠上皮细胞顶端膜，所以必不可少的哺乳动物锌稳态，已被发现。我们将hZTL 1鉴定为与基底外侧肠细胞锌转运蛋白ZnT 1具有同源性的人表达序列标签，并通过PCR推导出全长cDNA序列。该蛋白质由523个氨基酸组成，属于膜转运蛋白的阳离子扩散促进剂家族。不寻常的是，预测的拓扑结构包括12个而不是6个跨膜结构域。逆转录-PCR法检测ZTL1 mRNA在小鼠多种组织中的表达。Myc标记的hZTL1克隆在瞬时转染的极化人肠Caco-2细胞的顶膜处表达。在Caco-2细胞中的hZTL1 mRNA的表达增加与锌的营养培养基的补充，但是，在胎盘细胞系hZTL1似乎不受锌的调节。hZTL1在非洲爪蟾卵母细胞中的异源表达增加了跨质膜的锌摄取。hZTL1的定位、调节特性和功能表明其在调节饮食锌跨顶端肠上皮细胞膜吸收中的作用。
Zinc is essential to a wide range of cellular processes; therefore, it is important to elucidate the molecular mechanisms of zinc homeostasis. To date, no zinc transporters expressed at the enterocyte apical membrane, and so essential to mammalian zinc homeostasis, have been discovered. We identified hZTL1 as a human expressed sequence tag with homology to the basolateral enterocyte zinc transporter ZnT1 and deduced the full-length cDNA sequence by PCR. The protein of 523 amino acids belongs to the cation diffusion facilitator family of membrane transporters. Unusually, the predicted topology comprises 12 rather than 6 transmembrane domains. ZTL1 mRNA was detected by reverse transcription-PCR in a range of mouse tissues. A Myc-tagged hZTL1 clone was expressed in transiently transfected polarized human intestinal Caco-2 cells at the apical membrane. Expression of hZTL1 mRNA in Caco-2 cells increased with zinc supplementation of the nutrient medium; however, in the placental cell line JAR hZTL1 appeared not to be regulated by zinc. Heterologous expression of hZTL1 in Xenopus laevis oocytes increased zinc uptake across the plasma membrane. The localization, regulatory properties, and function of hZTL1 indicate a role in regulating the absorption of dietary zinc across the apical enterocyte membrane.