Zinc Transport: Regulation

AbstractZinc homeostasis in cells is tightly controlled within narrow boundaries through the highly integrated processes of zinc uptake, sequestration, and efflux across the cell membrane, which enable a variety of zinc‐dependent proteins and enzymes to play physiologically important roles in numerous and varied biological responses. Thus, zinc transport proteins are essential to these processes. In general, two solute carrier (SLC) transporters, ZnT and ZIP, primarily regulate zinc transport in metazoans, but other membrane proteins (such as permeable channels) are also involved in zinc transport. Zinc exists as a divalent cation under physiological conditions, and thus it is transported across the cell membrane in this state, unlike iron and copper, which are reduced or oxidized before or after transport. This feature of zinc suggests that the expression levels of active zinc transporters at the cellular sites where they normally operate are important for defining net zinc transport, and thus the regulated expression of zinc transporters is critical for systemic and cellular zinc homeostasis. Regulation of zinc transport by ZnT and ZIP transporters is achieved by the coordination of a number of processes such as posttranslational modifications, modulation of transporter expression, and trafficking and degradation, in a zinc‐dependent or a zinc‐independent manner. In both transporters, the conserved amino acid residues in the putative intramembranous zinc‐binding sites, which are essential for zinc transport activity, appear to be involved in zinc selectivity.