Zinc is a ubiquitous element welded into various metabolic, neurological, and immunological pathways. Here, Nishida et al. show how late-phase allergic responses rely on the zinc transporter Znt5, which shuttles zinc from the cytosol into the Golgi (page 1351).
Removing heavy metals, such as zinc, from mast cells disrupts their activation and blunts allergic responses. Now Nishida et al. show that Znt5 is dispensable for immediate allergic reactions, which are governed by degranulation, but is needed for late-phase allergic responses, which rely on cytokine production.
Without Znt5, protein kinase C (PKC) failed to translocate to the plasma membrane where it gets activated. And because PKC translocation drives NF-κB activation, NF-κB–dependent cytokine production was defective.
The zinc-finger motifs in PKC were required for PKC translocation. The authors suggest that the lack of Znt5 decreased the zinc that was available to bind to PKC in the Golgi.
Why the lack of Znt5 had no effect on degranulation is unclear, as this process also requires PKC translocation. The authors say that other independent pathways, perhaps triggered by a calcium flux, must have made up for the lack of zinc. Or, they suggest, the threshold of PKC activation required for degranulation might be lower than that for NF-κB activation.