Characterization of the GufA subfamily member SLC39A11/Zip11 as a zinc transporter
Characterization of the GufA subfamily member SLC39A11/Zip11 as a zinc transporter
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GufA 亚家族成员 SLC39A11/Zip11 作为锌转运蛋白的表征。
DOI：
10.1016/j.jnutbio.2013.02.010
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发表时间：
2013-10-01
影响因子：
5.6
通讯作者：
Wang, Fudi
中科院分区：
文献类型：
--
作者：
Yu, Yu;Wu, Aimin;Wang, Fudi
细胞锌的内流和外流是由两个主要的转运蛋白家族维持的，ZIP(SLC39A)和ZNT(SLC30A或CDF)分子。这一类中的一个分子ZIP11/SLC39A11的功能尚不清楚。通过对不同ZIP成员在真核生物和原核生物中的分布和进化关系的生物信息学分析表明，Zip11是一个古老的ZIP家族成员，可能起源于早期的真核生物祖先。小鼠Zip11基因在睾丸和胃、回肠、盲肠等消化系统中大量表达。分析细胞锌含量，金属硫蛋白水平，以及在高锌或低锌条件下的细胞活力，提示Zip11是一个锌进口体。此外，当Zip11被击倒时，细胞内锌浓度和金属硫蛋白水平下降。在补充锌的小鼠中，Zip11的mRNA和蛋白水平在几个组织中都略有上调。通过荧光素酶报告分析，Zip11第一外显子上游的金属反应元件序列(MRE)对细胞外锌浓度升高做出反应。诱变分析表明，一些MRE可以调节Zip11启动子的活性，金属反应转录因子-1(MTF-1)参与了这一过程。综上所述，这些数据表明，Zip11具有独特的蛋白质序列和结构特征，它具有细胞锌转运蛋白的功能，其表达至少部分受锌的调节，其表达是通过HMTF-1与Zip11启动子的MRE结合来实现的。(C)2013 Elsevier Inc.保留所有权利。
Cellular zinc influx and efflux are maintained by two major transporter families, the ZIP (SLC39A) and ZnT (SLC30A or CDF) molecules. The functions of one molecule in this class, ZIP11/SLC39A11, remain unclear. Bioinformatics analysis of the distribution and evolutionary relationships of different ZIP members in eukaryotes and prokaryotes indicated that Zip11, the sole member of gufA subfamily, is an ancient ZIP family member that might have originated in early eukaryotic ancestors. Murine Zip11 mRNA is abundantly expressed in testes and the digestive system including stomach, ileum and cecum. Analysis of cellular zinc content, metallothionein levels, and cell viability under high or low zinc conditions in cells transfected with a murine Zip11 expression plasmid, suggest that Zip11 is a zinc importer. Further, cellular zinc concentrations and metallothionein levels decreased when Zip11 was knocked down. In mice supplemented with zinc, both mRNA and protein levels of Zip11 were slightly up-regulated in several tissues. The metal response element sequences (MREs) upstream of the first exon of Zip11 responded to elevated extracellular zinc concentrations, as assessed by luciferase reporter assays. Mutagenic analysis showed that several of the MREs could regulate Zip11 promoter activity, and metal-responsive transcription factor-1 (MTF-1) was shown to be involved in this process. Collectively, these data suggest that Zip11 has unique protein sequence and structure features, it functions as a cellular zinc transporter, and its expression is at least partially regulated by zinc via hMTF-1 binding to MREs of the Zip11 promoter. (c) 2013 Elsevier Inc. All rights reserved.