title: Redox regulation of beta-actin during integrin-mediated cell adhesion.
abstract: Redox sensitivity of actin toward an exogenous oxidative stress has recently been reported. We report here the first evidence of in vivo actin redox regulation by a physiological source of reactive oxygen species, specifically those species generated by integrin receptors during cell adhesion. Actin oxidation takes place via the formation of a mixed disulfide between cysteine 374 and glutathione; this modification is essential for spreading and for cytoskeleton organization. Impairment of actin glutathionylation, either through GSH depletion or expression of the C374A redox-insensitive mutant, greatly affects cell spreading and the formation of stress fibers, leading to inhibition of the disassembly of the actinomyosin complex. These data suggest that actin glutathionylation is essential for cell spreading and cytoskeleton organization and that it plays a key role in disassembly of actinomyosin complex during cell adhesion.
authors.affiliation: Department of Biochemical Sciences, Center of Excellence for Scientific Research DENOTHE, Department of Anatomy, University of Florence, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Fiaschi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cozzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Raugei
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.forename: Giampietro
authors.initials: G
authors.lastname: Ramponi
authors.forename: Paola
authors.initials: P
authors.lastname: Chiarugi
mesh_terms: D000199:Actins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D003545:Cysteine / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010084:Oxidation-Reduction; D014945:Wound Healing
chemical_list: D000199:Actins; D016023:Integrins; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine