title: STIM1 juxtaposes ER to phagosomes, generating Ca²⁺ hotspots that boost phagocytosis.
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.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Paula
authors.initials: P
authors.lastname: Nunes
authors.forename: Daniela
authors.initials: D
authors.lastname: Cornut
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bochet
authors.forename: Udo
authors.initials: U
authors.lastname: Hasler
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Oh-Hora
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Waldburger
authors.forename: Nicolas
authors.initials: N
authors.lastname: Demaurex
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism*; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1; D019108:Tight Junctions
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium