Dufner-Beattie Jodi, Langmade S Joshua, Wang Fudi, Eide David, Andrews Glen K
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas 66160-7421, USA.
J Biol Chem. 2003 Dec 12;278(50):50142-50. doi: 10.1074/jbc.M304163200. Epub 2003 Oct 2.
Zinc is an essential metal for all eukaryotes, and cells have evolved a complex system of proteins to maintain the precise balance of zinc uptake, intracellular storage, and efflux. In mammals, zinc uptake appears to be mediated by members of the Zrt/Irt-like protein (ZIP) superfamily of metal ion transporters. Herein, we have studied a subfamily of zip genes (zip1, zip2, and zip3) that is conserved in mice and humans. These eight-transmembrane domain proteins contain a conserved 12-amino acid signature sequence within the fourth transmembrane domain. All three of these mouse ZIP proteins function to specifically increase the uptake of zinc in transfected cultured cells, similar to the previously demonstrated functions of human ZIP1 and ZIP2 (Gaither, L. A., and Eide, D. J. (2000) J. Biol. Chem. 275, 5560-5564; Gaither, L. A., and Eide, D. J. (2001) J. Biol. Chem. 276, 22258-22264). No ZIP3 orthologs have been previously studied. Furthermore, this first systematic comparative study of the in vivo expression and dietary zinc regulation of this subfamily of zip genes revealed that 1) zip1 mRNA is abundant in many mouse tissues, whereas zip2 and zip3 mRNAs are very rare or moderately rare, respectively, and tissue-restricted in their accumulation; and 2) unlike mouse metallothionein I and zip4 mRNAs (Dufner-Beattie, J., Wang, F., Kuo, Y.-M., Gitschier, J., Eide, D., and Andrews, G. K. (2003) J. Biol. Chem. 278, 33474-33481), the abundance of zip1, zip2, and zip3 mRNAs is not regulated by dietary zinc in the intestine and visceral endoderm, tissues involved in nutrient absorption. These studies suggest that all three of these ZIP proteins may play cell-specific roles in zinc homeostasis rather than primary roles in the acquisition of dietary zinc.
锌是所有真核生物必需的金属，细胞已经进化出一套复杂的蛋白质系统来维持锌摄取、细胞内储存和外排的精确平衡。在哺乳动物中，锌摄取似乎由金属离子转运蛋白的Zrt/Irt样蛋白（ZIP）超家族成员介导。在此，我们研究了在小鼠和人类中保守的zip基因亚家族（zip1、zip2和zip3）。这些含八个跨膜结构域的蛋白质在第四个跨膜结构域内含有一个保守的12个氨基酸的特征序列。这三种小鼠ZIP蛋白的功能均为特异性增加转染培养细胞中锌的摄取，类似于先前证明的人类ZIP1和ZIP2的功能（Gaither, L. A., and Eide, D. J. (2000) J. Biol. Chem. 275, 5560 - 5564; Gaither, L. A., and Eide, D. J. (2001) J. Biol. Chem. 276, 22258 - 22264）。此前尚未对ZIP3直系同源物进行过研究。此外，对该zip基因亚家族的体内表达和膳食锌调节的首次系统比较研究表明：1）zip1 mRNA在许多小鼠组织中丰富，而zip2和zip3 mRNA分别非常罕见或中度罕见，且在积累上具有组织限制性；2）与小鼠金属硫蛋白I和zip4 mRNA不同（Dufner - Beattie, J., Wang, F., Kuo, Y.-M., Gitschier, J., Eide, D., and Andrews, G. K. (2003) J. Biol. Chem. 278, 33474 - 33481），zip1、zip2和zip3 mRNA的丰度不受参与营养吸收的肠道和内脏内胚层中膳食锌的调节。这些研究表明，这三种ZIP蛋白可能在锌稳态中发挥细胞特异性作用，而不是在膳食锌摄取中发挥主要作用。
