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Title

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

Authors
Oh-Hora, Masatsugu
Published in Current Biology. 2012, vol. 22, p. 1-8
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 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.
Identifiers
PMID: 23041196
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Structures
Research groups Signaux intracellulaires (210)
Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
Mécanisme de l'inflammation articulaire (44)
Groupe Eric Féraille (néphrologie) (29)
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(ISO format)
NUNES, Paula et al. STIM1 Juxtaposes ER to Phagosomes, Generating Ca(2+) Hotspots that Boost Phagocytosis. In: Current Biology, 2012, vol. 22, p. 1-8. https://archive-ouverte.unige.ch/unige:26213

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Deposited on : 2013-02-05

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