New Galione group paper explores the role for early Ca2+ signals in phagocytosis

Macrophages clear pathogens by phagocytosis and lysosomes that fuse with phagosomes are traditionally regarded as to a source of membranes and luminal degradative enzymes. Here, we reveal that endo‐lysosomes act as platforms for a new phagocytic signalling pathway in which FcγR activation recruits the second messenger NAADP and thereby promotes the opening of Ca²⁺‐permeable two‐pore channels (TPC s). Remarkably, phagocytosis is driven by these local endo‐lysosomal Ca²⁺ nanodomains rather than global cytoplasmic or ER Ca²⁺ signals. Motile endolysosomes contact nascent phagosomes to promote phagocytosis, whereas endo‐lysosome immobilization prevents it. We show that TPC ‐released Ca²⁺ rapidly activates calcineurin, which in turn dephosphorylates and activates the GTP ase dynamin‐2. Finally, we find that different endo‐lysosomal Ca²⁺ channels play diverse roles, with TPC s providing a universal phagocytic signal for a wide range of particles and TRPML 1 being only required for phagocytosis of large targets.

See the full paper here: https://www.embopress.org/doi/10.15252/embj.2019104058