Figure 3.

Zn uptake via LTCC and ZnT5 controls the FcεRI-mediated delayed allergic response by mast cells. Zn is indispensable for FcεRI-mediated mast-cell activation. Upon antigen sensitization, LTCC (blue) on the ER membrane acts as a Zn gatekeeper and can rapidly increase the intracellular-free Zn levels in the perinuclear region dependent on calcium and MAPK/ERK signaling (Zn wave). The released Zn then regulates the DNA-binding activity of NF-κB followed by cytokine production. Simultaneously, ZnT5 (red) on the Golgi membrane takes up Zn to regulate the translocation of PKC to the plasma membrane. The resultant NF-κB activation induces inflammatory cytokine production. Thus, these Zn gatekeepers and Zn transporter control mast-cell-mediated, delayed-type allergic reactions.