title: Junctate boosts phagocytosis by recruiting endoplasmic reticulum Ca2+ stores near phagosomes.
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.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet, Geneva 4 CH-1211, Switzerland.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guido
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet, Geneva 4 CH-1211, Switzerland Nicolas.Demaurex@unige.ch Paula.Nunes@unige.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Demaurex
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet, Geneva 4 CH-1211, Switzerland Nicolas.Demaurex@unige.ch Paula.Nunes@unige.ch.
authors.forename: Paula
authors.initials: P
authors.lastname: Nunes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human; D002118:Calcium
keywords: Ca2+; Capacitive calcium entry; Ion channel; Junctate; Membrane contact site; Phagocytosis; Signal transduction