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Junctate boosts phagocytosis by recruiting endoplasmic reticulum Ca2+ stores near phagosomes

Published in Journal of Cell Science. 2015, vol. 128, no. 22, p. 4074-4082
Abstract Local intracellular Ca(2+) elevations increase the efficiency of phagocytosis, a process that is essential for innate and adaptive immunity. These local Ca(2+) elevations are generated in part by the store-operated Ca(2+) entry (SOCE) sensor STIM1, which recruits endoplasmic reticulum (ER) cisternae to phagosomes and opens phagosomal Ca(2+) channels at ER-phagosome junctions. However, residual ER-phagosome contacts and periphagosomal Ca(2+) hotspots remain in Stim1(-/-) cells. Here, we tested whether junctate (also called ASPH isoform 8), a molecule that targets STIM1 to ER-plasma-membrane contacts upon Ca(2+)-store depletion, cooperates with STIM1 at phagosome junctions. Junctate expression in Stim1(-/-) and Stim1(-/-); Stim2(-/-) phagocytic fibroblasts increased phagocytosis and periphagosomal Ca(2+) elevations, yet with only a minimal impact on global SOCE. These Ca(2+) hotspots were only marginally reduced by the SOCE channel blocker lanthanum chloride (La(3+)) but were abrogated by inositol trisphosphate receptor inhibitors 2-APB and xestospongin-C, revealing that unlike STIM1-mediated hotspots, junctate-mediated Ca(2+) originates predominantly from periphagosomal Ca(2+) stores. Accordingly, junctate accumulates near phagosomes and elongates ER-phagosome junctions in Stim1(-/-) cells. Thus, junctate mediates an alternative mechanism for generating localized Ca(2+) elevations within cells, promoting Ca(2+) release from internal stores recruited to phagosomes, thereby boosting phagocytosis.
Keywords AnimalsCalcium/metabolismCalcium-Binding Proteins/genetics/metabolismEndoplasmic Reticulum/metabolismHumansMembrane Proteins/genetics/metabolismMiceMixed Function Oxygenases/genetics/metabolismMuscle Proteins/genetics/metabolismPhagocytosis/physiologyPhagosomes/metabolismSignal Transduction
PMID: 26446257
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Article (Published version) (1.2 MB) - public document Free access
Research groups Signaux intracellulaires (210)
Mécanismes de la présentation croisée des antigènes (1011)
Project FNS: 31003A_149566
(ISO format)
GUIDO, Danièle, DEMAUREX, Nicolas, NUNES-HASLER, Paula. Junctate boosts phagocytosis by recruiting endoplasmic reticulum Ca2+ stores near phagosomes. In: Journal of Cell Science, 2015, vol. 128, n° 22, p. 4074-4082. doi: 10.1242/jcs.172510 https://archive-ouverte.unige.ch/unige:88513

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Deposited on : 2016-11-01

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