hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells
hZip1 (hSLC39A1) regulates zinc homoeostasis in gut epithelial cells
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DOI：
10.1007/s12263-013-0332-z
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Ackland, M. Leigh
中科院分区：
文献类型：
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作者：
Michalczyk, Agnes A.;Ackland, M. Leigh
锌是酶催化、基因调控和信号转导所必需的微量元素。锌的吸收发生在小肠;然而，细胞积累锌的机制并不完全清楚。Zip 1（SLC 39 A1）是一种预测的跨膜蛋白，被假定但尚未最终证明介导肠道细胞中的锌内流。本研究的目的是探讨hZip 1在介导人类肠上皮细胞锌摄取中的作用。在人肠组织中检测到hZip 1 mRNA和蛋白。在未分化的Caco-2人肠细胞中，hZip 1部分定位于内质网。相反，在分化的Caco-2细胞培养的细胞外基质中，hZip 1蛋白位于接近顶端微绒毛。缺乏表面抗体结合和内化表明hZip 1不存在于质膜上。使用Zn-65进行了功能研究，以确定hZip 1在细胞锌积累中的作用。在Caco-2细胞窝藏hZip 1过表达的构建体，细胞锌积累相对于对照增强。相反，具有hZip 1 siRNA构建体的Caco-2细胞显示锌积累减少。总之，我们表明，Caco-2细胞分化支持靶向的hZip 1的顶端域附近的区域。由于没有hZip 1在顶端质膜，我们建议，hZip 1可以作为一个细胞内传感器，以调节锌稳态在人类肠道细胞。
Zinc is an essential trace element required for enzyme catalysis, gene regulation and signal transduction. Zinc absorption takes place in the small intestine; however, the mechanisms by which cells accumulate zinc are not entirely clear. Zip1 (SLC39A1) is a predicted transmembrane protein that is postulated, but not conclusively proven to mediate zinc influx in gut cells. The aim of this study was to investigate a role for hZip1 in mediating zinc uptake in human enterocytes. Both hZip1 mRNA and protein were detected in human intestinal tissue. In non-differentiated Caco-2 human gut cells, hZip1 was partially localised to the endoplasmic reticulum. In contrast, in differentiated Caco-2 cells cultured in extracellular matrix, the hZip1 protein was located in proximity to the apical microvilli. Lack of surface antibody binding and internalisation indicated that hZip1 was not present on the plasma membrane. Functional studies to establish a role for hZip1 in cellular zinc accumulation were carried out using Zn-65. In Caco-2 cells harbouring an hZip1 overexpression construct, cellular zinc accumulation was enhanced relative to the control. Conversely, Caco-2 cells with an hZip1 siRNA construct showed reduced zinc accumulation. In summary, we show that the Caco-2 cell differentiation endorses targeting of hZip1 to a region near the apical domain. Given the absence of hZip1 at the apical plasma membrane, we propose that hZip1 may act as an intracellular sensor to regulate zinc homoeostasis in human gut cells.