title: Regulation of the ROS response dynamics and organization to PDGF motile stimuli revealed by single nanoparticle imaging.
abstract: Although reactive oxygen species (ROS) are better known for their harmful effects, more recently, H2O2, one of the ROS, was also found to act as a secondary messenger. However, details of spatiotemporal organization of specific signaling pathways that H2O2 is involved in are currently missing. Here, we use single nanoparticle imaging to measure the local H2O2 concentration and reveal regulation of the ROS response dynamics and organization to platelet-derived growth factor (PDGF) signaling. We demonstrate that H2O2 production is controlled by PDGFR kinase activity and EGFR transactivation, requires a persistent stimulation, and is regulated by membrane receptor diffusion. This temporal filtering is impaired in cancer cells, which may determine their pathological migration. H2O2 subcellular mapping reveals that an external PDGF gradient induces an amplification-free asymmetric H2O2 concentration profile. These results support a general model for the control of signal transduction based only on membrane receptor diffusion and second messenger degradation.
authors.affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France. Electronic address: cedric.bouzigues@polytechnique.edu.
authors.forename: Cedric I
authors.initials: CI
authors.lastname: Bouzigues
authors.affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France.
authors.forename: Thanh-Liêm
authors.initials: TL
authors.lastname: Nguyên
authors.affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France.
authors.forename: Rivo
authors.initials: R
authors.lastname: Ramodiharilafy
authors.affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France.
authors.forename: Amy
authors.initials: A
authors.lastname: Claeson
authors.affiliation: Paris Cardiovascular Research Center, Inserm U 970, 75015 Paris, France.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Tharaux
authors.affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique Université Paris Saclay, Inserm U696, CNRS 7645, 91128 Palaiseau, France.
authors.forename: Antigoni
authors.initials: A
authors.lastname: Alexandrou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010982:Platelet-Derived Growth Factor; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide