Authors
Jorge J Pinilla-Tenas, Brian K Sparkman, Ali Shawki, Anthony C Illing, Colin J Mitchell, Ningning Zhao, Juan P Liuzzi, Robert J Cousins, Mitchell D Knutson, Bryan Mackenzie
Publication date
2011/10
Journal
American Journal of Physiology-Cell Physiology
Volume
301
Issue
4
Pages
C862-C871
Publisher
American Physiological Society
Description
Recent studies have shown that overexpression of the transmembrane protein Zrt- and Irt-like protein 14 (Zip14) stimulates the cellular uptake of zinc and nontransferrin-bound iron (NTBI). Here, we directly tested the hypothesis that Zip14 transports free zinc, iron, and other metal ions by using the Xenopus laevis oocyte heterologous expression system, and use of this approach also allowed us to characterize the functional properties of Zip14. Expression of mouse Zip14 in RNA-injected oocytes stimulated the uptake of 55Fe in the presence of l-ascorbate but not nitrilotriacetic acid, indicating that Zip14 is an iron transporter specific for ferrous ion (Fe2+) over ferric ion (Fe3+). Zip14-mediated 55Fe2+ uptake was saturable (K0.5 ≈ 2 μM), temperature-dependent (apparent activation energy, Ea = 15 kcal/mol), pH-sensitive, Ca2+-dependent, and inhibited by Co2+, Mn2+, and Zn2+. HCO3 stimulated 55Fe2+ transport …
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