UNIGE document Scientific Article
previous document  unige:26213  next document
add to browser collection

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

Cornut, Daniela
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.
PMID: 23041196
Full text
Article (Author postprint) (2.2 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research groups Signaux intracellulaires (210)
Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
Mécanisme de l'inflammation articulaire (44)
Groupe Eric Féraille (néphrologie) (29)
(ISO format)
NUNES-HASLER, 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

327 hits



Deposited on : 2013-02-05

Export document
Format :
Citation style :