Phosphoinositol 3-phosphate acts as a timer for reactive oxygen species production in the phagosome
| Autor: | Leïla Bouchab, Romain Le Bars, Sophie Dupré-Crochet, Elodie Hudik, Zhi Min Song, Oliver Nüsse |
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| Přispěvatelé: | Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Microscopie Photonique (PHOT), Département Plateforme (PF I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Neutrophils [SDV]Life Sciences [q-bio] Phagocytosis Primary Cell Culture Immunology Phosphatase Autophagy-Related Proteins Monocytes 03 medical and health sciences Phosphatidylinositol Phosphates Cell Line Tumor Phagosomes Humans Immunology and Allergy RNA Small Interfering Phagosome chemistry.chemical_classification Oxidase test Reactive oxygen species Gene knockdown NADPH oxidase biology Intracellular Signaling Peptides and Proteins NADPH Oxidases Intracellular Membranes Cell Biology Phosphoproteins Protein Tyrosine Phosphatases Non-Receptor Cell biology Cytosol 030104 developmental biology Gene Expression Regulation chemistry biology.protein Reactive Oxygen Species Signal Transduction |
| Zdroj: | Journal of Leukocyte Biology Journal of Leukocyte Biology, 2017, pp.jlb.1A0716--305R. ⟨10.1189/jlb.1A0716-305R⟩ |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | 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 p40phox by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40phox and p67phox at 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 p40phox from 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 p67phox at 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 p40phox and p67phox at the phagosomal membrane. |
| Databáze: | OpenAIRE |
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