Cd2+ versus Zn2+ uptake by the ZIP8 HCO3--dependent symporter: kinetics, electrogenicity and trafficking.
The mouse Slc39a8 gene encodes the ZIP8 transporter, which has been shown to be a divalent cation/HCO3- symporter. Using ZIP8 cRNA-injected Xenopus oocyte cultures, we show herein that: [a] ZIP8-mediated cadmium (Cd(2+)) and zinc (Zn(2+)) uptake have V(max) values of 1.8+/-0.08 and 1.0+/-0.08 pmol/oocyte/h, and K(m) values of 0.48+/-0.08 and 0.26+/-0.09 microM, respectively; [b] ZIP8-mediated Cd(2+) uptake is most inhibited by Zn(2+), second-best inhibited by Cu(2+), Pb(2+) and Hg(2+), and not inhibited by Mn(2+) or Fe(2+); and [c] electrogenicity studies demonstrate an influx of two HCO3- anions per one Cd(2+) (or one Zn(2+)) cation, i.e. electroneutral complexes. Using Madin-Darby canine kidney (MDCK) polarized epithelial cells retrovirally infected with ZIP8 cDNA and tagged with hemagglutinin at the C-terminus, we show that-similar to ZIP4-the ZIP8 eight-transmembrane protein is largely internalized during Zn(2+) homeostasis, but moves predominantly to the cell surface membrane (trafficking) under conditions of Zn(2+) depletion.
Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267-0056, USA.
Zhiwei
Z
Liu
Hong
H
Li
Manoocher
M
Soleimani
Kuppuswami
K
Girijashanker
Jodie M
JM
Reed
Lei
L
He
Timothy P
TP
Dalton
Daniel W
DW
Nebert
D000818:Animals; D002104:Cadmium / Q000493:pharmacokinetics*; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D015032:Zinc / Q000493:pharmacokinetics*
D027682:Cation Transport Proteins; C499256:Slc39a8 protein, mouse; D002104:Cadmium; D015032:Zinc