Zn(2+) at a cellular crossroads

Abstract

Zinc is an essential micronutrient for cellular homeostasis. Initially proposed to only contribute to cellular viability through structural roles and non-redox catalysis, advances in quantifying changes in nM and pM quantities of Zn(2+) have elucidated increasing functions as an important signaling molecule. This includes Zn(2+)-mediated regulation of transcription factors and subsequent protein expression, storage and release of intracellular compartments of zinc quanta into the extracellular space which modulates plasma membrane protein function, as well as intracellular signaling pathways which contribute to the immune response. This review highlights some recent advances in our understanding of zinc signaling.

Figure 1

A representation of extracellular Zn²⁺ signaling pathways. Zn²⁺ released into the extracellular space between cells can interact with proteins on the surface of another cell. Zn²⁺-binding can initiate a variety of responses including the release of Ca²⁺, another signaling metal ion. For example, signaling between neurons occurs when Zn²⁺ is released from vesicles in the presynaptic neuron into the synapse. Interactions between Zn²⁺ and protein receptors on the postsynaptic neuron are the next step in the signaling cascade.

Figure 2

A representation of various intracellular Zn²⁺ signals. In fast Zn²⁺ signa ling (i), binding of an extracellular ligand can trigger the release of Zn²⁺ from intracellular stores, liberation of Zn²⁺ from MTs by oxidative processes or flow of Zn²⁺ through permeable channels. Interaction of Zn²⁺ with target receptors that occurs before homeostasis is restored, constitutes a signaling pathway. Alternatively, in late Zn²⁺ signaling (ii), import and export by proteins changes the intracellular concentrations, which triggers transcriptional regulation of the homeostasis machinery.