Zinc in Cellular Regulation: The Nature and Significance of “Zinc Signals”

In the last decade, we witnessed discoveries that established Zn(2+) as a second major signalling metal ion in the transmission of information within cells and in communication between cells. Together with Ca(2+) and Mg(2+), Zn(2+) covers biological regulation with redox-inert metal ions over many orders of magnitude in concentrations. The regulatory functions of zinc ions, together with their functions as a cofactor in about three thousand zinc metalloproteins, impact virtually all aspects of cell biology. This article attempts to define the regulatory functions of zinc ions, and focuses on the nature of zinc signals and zinc signalling in pathways where zinc ions are either extracellular stimuli or intracellular messengers. These pathways interact with Ca(2+), redox, and phosphorylation signalling. The regulatory functions of zinc require a complex system of precise homeostatic control for transients, subcellular distribution and traffic, organellar homeostasis, and vesicular storage and exocytosis of zinc ions.