ER connections boost phagocytosis

Phagocytosis is important for the uptake of nutrients and for the removal of pathogens and cell debris by the immune system. High Ca²⁺ levels at the phagosome boost phagocytosis, but the mechanisms driving these Ca²⁺ increases are unclear. Here Nunes et al. show that stromal interaction molecule 1 (STIM1), an endoplasmic reticulum (ER) Ca²⁺ sensor that interacts with and activates plasma membrane Ca²⁺ channels, promotes the formation of tight phagosome–ER junctions in mouse fibroblasts and neutrophils, and that this generates localized Ca²⁺ rises. Furthermore, they find that signalling-deficient STIM1 can still promote the recruitment of the ER to the phagosome but cannot induce Ca²⁺ hotspots and phagocytosis. This suggests that STIM1 signals the opening of phagosomal Ca²⁺ channels and also sheds light on the functional significance of ER remodelling during phagocytosis.