STIM1 Juxtaposes ER to Phagosomes, Generating Ca(2+) Hotspots that Boost Phagocytosis

Article Article scientifique Article STIM1 Juxtaposes ER to Phagosomes, Generating Ca(2+) Hotspots that Boost Phagocytosis eng 2012 author Nunes-Hasler Paula 0000-0002-4598-685X 707324 author Cornut Daniela author Bochet Vanessa 649744 author Hasler Udo 134082 author Oh-Hora Masatsugu author Waldburger Jean-Marc 81557 author Demaurex Nicolas 0000-0002-9933-6772 24642 1-8 10.1016/j.cub.2012.08.049 23041196 0960-9822 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 Ca(2+) 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 Ca(2+) depletion in mouse neutrophils, and exogenous YFP-STIM1 puncta coincided with localized Ca(2+) elevations around phagosomes in fibroblasts expressing phagocytic receptors. STIM1 ablation decreased phagocytosis, ER-phagosome contacts, and periphagosomal Ca(2+) 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 Ca(2+) depletion and increased the shedding of periphagosomal actin rings. Re-expression of a signaling-deficient STIM1 mutant unable to open Ca(2+) channels recruited ER cisternae to the vicinity of phagosomes but failed to rescue phagocytosis, actin shedding, and periphagosomal Ca(2+) elevations. The periphagosomal Ca(2+) hotspots were decreased by extracellular Ca(2+) chelation and by Ca(2+) channels inhibitors, revealing that the Ca(2+) 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 Ca(2+) elevations that promote high-efficiency phagocytosis. Dewey 612 Dewey 616.07 134 Département de physiologie cellulaire et métabolisme 21C 137 Département de pathologie et immunologie 21F false 579 Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) 922 20 Laboratoire de physiologie et pathophysiologie des cellules rénales 29 28 Inflammation articulaire 44 1293 Mécanismes de la présentation croisée des antigènes 1011 168 Signaux intracellulaires 210 Current biology 22 207886a8-38cb-4a0b-b9b9-219987a1c755 Article (Accepted version) Restricted curbio9840_4d3ky7.pdf 2261497 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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STIM1 Juxtaposes ER to Phagosomes, Generating Ca(2+) Hotspots that Boost Phagocytosis	Current biology			2012	709	5

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Bochet, Vanessa