title: Reactive oxygen species regulate protrusion efficiency by controlling actin dynamics.
abstract: Productive protrusions allowing motile cells to sense and migrate toward a chemotactic gradient of reactive oxygen species (ROS) require a tight control of the actin cytoskeleton. However, the mechanisms of how ROS affect cell protrusion and actin dynamics are not well elucidated yet. We show here that ROS induce the formation of a persistent protrusion. In migrating epithelial cells, protrusion of the leading edge requires the precise regulation of the lamellipodium and lamella F-actin networks. Using fluorescent speckle microscopy, we showed that, upon ROS stimulation, the F-actin retrograde flow is enhanced in the lamellipodium. This event coincides with an increase of cofilin activity, free barbed ends formation, Arp2/3 recruitment, and ERK activity at the cell edge. In addition, we observed an acceleration of the F-actin flow in the lamella of ROS-stimulated cells, which correlates with an enhancement of the cell contractility. Thus, this study demonstrates that ROS modulate both the lamellipodium and the lamella networks to control protrusion efficiency.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Taulet
authors.forename: Violaine D
authors.initials: VD
authors.lastname: Delorme-Walker
authors.forename: Céline
authors.initials: C
authors.lastname: DerMardirossian
mesh_terms: D051339:Actin Depolymerizing Factors / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014335:Tropomyosin / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D017382:Reactive Oxygen Species; D014335:Tropomyosin; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D024507:Nonmuscle Myosin Type IIA