title: Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome.
abstract: Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40phoxby an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40phoxand p67phoxat the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils. It also releases p67phox, the key cytosolic subunit of the oxidase, and p40phoxfrom the phagosome. The knockdown of the PI(3)P phosphatase MTM1 or Rubicon or both increases the level of PI(3)P at the phagosome. That increase enhances ROS production inside the phagosome and triggers an extended accumulation of p67phoxat the phagosome. Furthermore, the overexpression of MTM1 at the phagosomal membrane induces the disappearance of PI(3)P from the phagosome and prevents sustained ROS production. In conclusion, PI(3)P, indeed, regulates ROS production by maintaining p40phoxand p67phoxat the phagosomal membrane.
authors.affiliation: Université Paris-Sud and Université Paris-Saclay, Orsay, France.|CNRS, LCP, Orsay, France.|INSERM U1174, Orsay, France; and.
authors.forename: Zhi Min
authors.initials: ZM
authors.lastname: Song
authors.affiliation: Université Paris-Sud and Université Paris-Saclay, Orsay, France.|CNRS, LCP, Orsay, France.|INSERM U1174, Orsay, France; and.
authors.forename: Leïla
authors.initials: L
authors.lastname: Bouchab
authors.affiliation: Université Paris-Sud and Université Paris-Saclay, Orsay, France.|CNRS, LCP, Orsay, France.|INSERM U1174, Orsay, France; and.
authors.forename: Elodie
authors.initials: E
authors.lastname: Hudik
authors.affiliation: Imagerie-Gif Cell Biology Pole, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud and Université Paris-Saclay, Gif-sur-Yvette cedex, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Le Bars
authors.affiliation: Université Paris-Sud and Université Paris-Saclay, Orsay, France.|CNRS, LCP, Orsay, France.|INSERM U1174, Orsay, France; and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Nüsse
authors.affiliation: Université Paris-Sud and Université Paris-Saclay, Orsay, France; sophie.dupre@u-psud.fr.|CNRS, LCP, Orsay, France.|INSERM U1174, Orsay, France; and.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dupré-Crochet
mesh_terms: D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010588:Phagosomes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C552537:RUBCN protein, human; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; C055525:phosphatidylinositol 3-phosphate; D019255:NADPH Oxidases; C113333:NCF4 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C099588:myotubularin
keywords: NADPH oxidase; live imaging; phagocytosis