Received for publication November 20, 2007.
Revised February 12, 2008.
Accepted for publication February 12, 2008.

Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter

Abstract

The mouse and human genomes contain 14 highly conserved SLC39 genes. Evolutionarily, SLC39A14 and SLC39A8 are most closely related, both having three noncoding exons 1. However, the SLC39A14 has two exons 4, giving rise to ZIP14A and ZIP14B alternatively-spliced products. C57BL/6J mouse ZIP14A expression is highest in liver, duodenum, kidney and testis; ZIP14B expression is highest in liver, duodenum, brain and testis; ZIP8 is highest in lung, testis and kidney. We studied ZIP14 stably retroviral-infected mouse fetal fibroblast cultures (rvZIP) and transiently transfected Madin-Darby canine kidney (MDCK) polarized epithelial cells. Our findings include: [a] ZIP14-mediated cadmium uptake is proportional to cell toxicity, while manganese is not; [b] ZIP14B has a higher affinity than ZIP14A toward Cd²⁺ (Km = 0.14 vs 1.1 µM) and Mn²⁺ uptake (Km = 4.4 vs 18.2 µM); [c] ZIP14A- and ZIP14B-mediated Cd²⁺ uptake is most inhibited by Zn²⁺, and next by Mn²⁺ and Cu²⁺; [d] like ZIP8, ZIP14A- and ZIP14B-mediated Cd²⁺ uptake is dependent on extracellular HCO₃^-; [e] like ZIP8, ZIP14 transporters are localized on the apical surface of MDCK-ZIP cells; and [f] like ZIP8, ZIP14 proteins are glycosylated. Tissues such as intestine and liver, located between the environment and the animal, show high levels of ZIP14; given the high affinity for ZIP14, Cd²⁺ is likely to act as a rogue hitchhiker¡V¡Vdisplacing Zn²⁺ or Mn²⁺ and entering the body to cause unwanted cell damage and disease.

Key words: Ion transporters (SERCA, Na/K ATPase, CFTR), Liver transporters, Genetics, Metals and chelators

This article has been cited by other articles:

				T. Kambe, J. Geiser, B. Lahner, D. E. Salt, and G. K. Andrews Slc39a1 to 3 (subfamily II) Zip genes in mice have unique cell-specific functions during adaptation to zinc deficiency Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1474 - R1481. [Abstract] [Full Text] [PDF]