Functional expression of the human hZIP2 zinc transporter

Zinc is an essential nutrient for humans, yet we know little about how this metal ion is taken up by mammalian cells. In this report, we describe the characterization of hZip2, a human zinc transporter identified by its simil arity to zinc transporters recently characterized in fungi and plants. hZip 2 is a member of the ZIP family of eukaryotic metal ion transporters that i ncludes two other human genes, hZIP1 and hZIP3, and genes in mice and rats. To test whether hZip2 is a zinc transporter, we examined Zn-65 uptake acti vity in transfected K562 erythroleukemia cells expressing hZip2 from the CM V promoter. hZip2-expressing cells accumulated more zinc than control cells because of an increased initial zinc uptake rate. This activity was time-, temperature-, and concentration-dependent and saturable with an apparent K -m of 3 mu M. hZip2 zinc uptake activity was inhibited by several other tra nsition metals, suggesting that this protein may transport other substrates as R-ell. hZip2 activity was not energy-dependent, nor did it require K+ o r Na+ gradients. Zinc uptake by hZip2 was stimulated by HCO3- treatment, su ggesting a Zn2+-HCO3- cotransport mechanism. Finally, hZip2 was exclusively localized in the plasma membrane. These results indicate that hZip2 is a z inc transporter, and its identification provides one of the first molecular tools to study zinc uptake in mammalian cells.