Roles of zinc transporters in cellular transport of cadmium and manganese

Abstract

As cadmium (Cd) is a nonessential metal, there is no specific transport system for cellular entry of Cd in the organisms. The establishment of Cd-resistant cells from metallothionein-null mouse cells, application of multi-tracer technique, and microarray analyses have revealed that Cd2+ shares the pathway for cellular incorporation with Mn2+, and the responsible transporters for this pathway were found to be ZIP8 (Zrt- and Irt-related protein 8) and ZIP14. Although other transport systems for iron or calcium are also utilized for cellular incorporation of Cd2+ and Mn2+, characterization of ZIP8 and ZIP14 has demonstrated important physiological and pathological roles of these transporters in metal transport. We show here the significant roles of ZIP8 in segment-specific transport of Cd in proximal tubule of the kidney and the roles of ZIP14 and ZnT10 in Mn transport in neuronal cells in the presence of cytokine. Recently, critical roles of Mn transport systems have been highlighted by the findings of human diseases related to the mutation in ZIP8 and ZnT10. This chapter summarized historical background and recent advances in the studies on the roles of ZIP8 and ZIP14 in the transport of Cd2+ and Mn2+.