Stromal interaction molecule 1 (STIM1) mediates global store-operated Ca2+ entry (SOCE) and local, endoplasmic reticulum (ER)-derived elevation of Ca2+, both of which are important for phagosome maturation. However, cells derived from Stim1−/− mice still have residual Ca2+ hotspots. In this issue (p. ), Paula Nunes, Nicolas Demaurex and Daniele Guido provide a conceptually new alternative mechanism for the generation of localised Ca2+ hotspots that are mediated by junctate – a STIM1 interactor known to function in Ca2+ homeostasis. The authors find that junctate can be recruited to phagosomes independently of STIM1 and its overexpression results in doubling the number of phagocytosed particles per cell, regardless of whether STIM proteins are present or not. Surprisingly, although the overexpression of either junctate or STIM1 produces the same significant increase in peri-phagosomal Ca2+ hotspots in Stim1−/− cells, junctate overexpression has only a modest effect on global SOCE in STIM-depleted cells. Furthermore, in contrast to STIM1, which affects both Ca2+-containing ER cisternae and Ca2+ channels at the phagosomal membrane, junctate only triggers release from intracellular Ca2+ stores that are sensitive to inositol (1,4,5)-trisphosphate. These data suggest that junctate can replace STIM1 in the process of recruiting intracellular Ca2+ stores to phagosomes, without having an effect on global SOCE. As such, junctate emerges as a facilitator necessary for an alternative mechanism to mobilise and release Ca2+ that might be of crucial importance when STIM1 is targeted in cancer and other diseases.
