Figure 13.

Summary of the proposed local interactome between ancient immune molecules that reside in the mast cells of fish: histidine-rich piscidin peptides, heparin, and Cu²⁺. The schematic illustration of the mast cells includes the nucleus (dark blue) and histamine, which is derived from histidine. Piscidins, which contain histidines and an ATCUN motif, are pH-sensitive and coordinate Cu²⁺. These cationic AMPs experience interactions with heparin that are in the micromolar range relevant to their FPR-mediated chemotactic activity following degranulation and bacterial killing in acidic phagosomes (orange) or extracellularly. Cu²⁺, which enhances the antimicrobial activity of piscidins, regulates their interactions with heparin and FPRs (purple). In particular, it increases FPR desensitization and aggregation back in the cells, an effect that is not altered by the presence of heparin.