The mammalian Zip5 protein is a zinc transporter that localizes to the basolateral surface of polarized cells.
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.
Departments of Biochemistry and Nutritional Sciences, University of Missouri, Columbia, Missouri 65211, USA.
Fudi
F
Wang
Byung-Eun
BE
Kim
Michael J
MJ
Petris
David J
DJ
Eide
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D002412:Cations; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005029:Ethylenediamines / Q000494:pharmacology; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000378:metabolism; D007477:Ions; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D015032:Zinc / Q000737:chemistry*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002412:Cations; D002614:Chelating Agents; D005029:Ethylenediamines; D007477:Ions; D012333:RNA, Messenger; C477530:Slc39a4 protein, mouse; C494728:Slc39a5 protein, mouse; C017800:zinc-binding protein; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine