STIM1 juxtaposes ER to phagosomes, generating Ca2+ hotspots that boost phagocytosis

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Abstract

Background: Endoplasmic reticulum (ER) membranes are recruited to phagosomes, but the mechanism and functional significance of this ER recruitment is not known. Here, we show that the ER Ca2+ sensor stromal interaction molecule 1 (STIM1) sustains high-efficiency phagocytosis by recruiting thin ER cisternae that interact productively but do not fuse with phagosomes. Results: Endogenous STIM1 was recruited to phagosomes upon ER Ca2+ depletion in mouse neutrophils, and exogenous YFP-STIM1 puncta coincided with localized Ca2+ elevations around phagosomes in fibroblasts expressing phagocytic receptors. STIM1 ablation decreased phagocytosis, ER-phagosome contacts, and periphagosomal Ca2+ elevations in both neutrophils and fibroblasts, whereas STIM1 re-expression in Stim1-/- fibroblasts rescued these defects, promoted the formation and elongation of tight ER-phagosome contacts upon ER Ca2+ depletion and increased the shedding of periphagosomal actin rings. Re-expression of a signaling-deficient STIM1 mutant unable to open Ca2+ channels recruited ER cisternae to the vicinity of phagosomes but failed to rescue phagocytosis, actin shedding, and periphagosomal Ca2+ elevations. The periphagosomal Ca2+ hotspots were decreased by extracellular Ca 2+ chelation and by Ca2+ channels inhibitors, revealing that the Ca2+ ions originate at least in part from phagosomes. Conclusions: Our findings indicate that STIM1 recruits ER cisternae near phagosomes for signaling purposes and that the opening of phagosomal Ca 2+ channels generates localized Ca2+ elevations that promote high-efficiency phagocytosis. © 2012 Elsevier Ltd.

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Nunes, P., Cornut, D., Bochet, V., Hasler, U., Oh-Hora, M., Waldburger, J. M., & Demaurex, N. (2012). STIM1 juxtaposes ER to phagosomes, generating Ca2+ hotspots that boost phagocytosis. Current Biology, 22(21), 1990–1997. https://doi.org/10.1016/j.cub.2012.08.049

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