Zinc has always had its fingers in the structure and activity of enzymes, transcription factors, and signaling molecules. Now, Yamasaki et al. (page 637) find zinc also working as a second messenger capable of converting an external signal into internal events.
When the authors created an external signal in mast cells by cross-linking IgE receptors, they observed an internal wave of free zinc released from the vicinity of the ER. Calcium and activated MAP kinase were necessary for the wave, which took several minutes to occur, in contrast to rapid calcium releases.
Cranking up the levels of free zinc prolonged the expression of cytokines IL-6 and TNFα—late stages of IgE signaling—and vice versa. Higher zinc also enhanced tyrosine phosphorylation levels, so zinc may boost signaling efficiency by inhibiting phosphatase activity.
The precise origin of the wave and how zinc stores are released remain a mystery, as do the downstream targets of the free zinc. Another important step will be to determine whether zinc wave signaling is a general phenomenon or is specific to mast cells. The zinc wave could be a potent addition to the cell's limited second messenger repertoire, as 2–3% of total cell proteins have zinc-binding domains.