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Originally published In Press as doi:10.1074/jbc.M408361200 on August 20, 2004

J. Biol. Chem., Vol. 279, Issue 49, 51433-51441, December 3, 2004
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The Mammalian Zip5 Protein Is a Zinc Transporter That Localizes to the Basolateral Surface of Polarized Cells*

Fudi Wang, Byung-Eun Kim, Michael J. Petris, and David J. Eide{ddagger}

From the Departments of Biochemistry and Nutritional Sciences, University of Missouri, Columbia, Missouri 65211

The mouse and human Zip5 proteins are members of the ZIP family of metal ion transporters. In this study, we present evidence that mouse Zip5 is a zinc uptake transporter that is specific for Zn(II) over other potential metal ion substrates. We also show that, unlike many other mammalian ZIP proteins, the endocytic removal of mZip5 from the plasma membrane is not triggered by zinc treatment. Thus, the activity of mZip5 does not appear to be down-regulated by zinc repletion. Zip5 expression is restricted to many tissues important for zinc homeostasis, including the intestine, pancreas, liver, and kidney. Zip5 is similar in sequence to the Zip4 protein, which is involved in the uptake of dietary zinc. Co-expression of Zip4 and Zip5 in the intestine led to the hypothesis that these proteins play overlapping roles in the uptake of dietary zinc across the apical membrane of intestinal enterocytes. Surprisingly, however, we found that mZip5 localizes specifically to the basolateral membrane of polarized Madin-Darby canine kidney cells. These observations suggest that Zip5 plays a novel role in polarized cells by carrying out serosal-to-mucosal zinc transport. Furthermore, given its expression in tissues important to zinc homeostasis, we propose that Zip5 plays a central role in controlling organismal zinc status.


Received for publication, July 23, 2004 , and in revised form, August 9, 2004.

* This work was supported by National Institutes of Health Grant DK50181 (awarded to Glen K. Andrews, University of Kansas Medical Center, and D. J. E.) and Grant GM56285 (to D. J. E.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: Dept. of Nutritional Sciences, 340B Nutritional Sciences, 1415 Linden Dr., University of Wisconsin, Madison, WI 53706. Tel.: 608-263-1613; Fax: 608-262-5860; E-mail: eide{at}nutrisci.wisc.edu.


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