How cellular Zn signaling drives physiological functions.

Zinc is an essential micronutrient affecting many aspects of human health. Cellular Zn homeostasis is critical for cell function and survival. Zn, acting as a first or second messenger, triggers signaling pathways that mediate the physiological roles of Zn. Transient changes in Zn concentrations within the cell or in the extracellular region occur following its release from Zn binding metallothioneins, its transport across membranes by the ZnT or ZIP transporters, or release of vesicular Zn. These transients activate a distinct Zn sensing receptor, ZnR/GPR39, or modulate numerous proteins and signaling pathways. Importantly, Zn signaling regulates cellular physiological functions such as: proliferation, differentiation, ion transport and secretion. Indeed, novel therapeutic approaches aimed to maintain Zn homeostasis and signaling are evolving. This review focuses on recent findings describing roles of Zn and its transporters in regulating physiological or pathological processes.