How cellular Zn²⁺ signaling drives physiological functions

Zinc is an essential micronutrient affecting many aspects of human health. Cellular Zn ²⁺ homeostasis is critical for cell function and survival. Zn ²⁺ , acting as a first or second messenger, triggers signaling pathways that mediate the physiological roles of Zn ²⁺ . Transient changes in Zn ²⁺ concentrations within the cell or in the extracellular region occur following its release from Zn ²⁺ binding metallothioneins, its transport across membranes by the ZnT or ZIP transporters, or release of vesicular Zn ²⁺ . These transients activate a distinct Zn ²⁺ sensing receptor, ZnR/GPR39, or modulate numerous proteins and signaling pathways. Importantly, Zn ²⁺ signaling regulates cellular physiological functions such as: proliferation, differentiation, ion transport and secretion. Indeed, novel therapeutic approaches aimed to maintain Zn ²⁺ homeostasis and signaling are evolving. This review focuses on recent findings describing roles of Zn ²⁺ and its transporters in regulating physiological or pathological processes.