Redox regulation of beta-actin during integrin-mediated cell adhesion.
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.
Fiaschi
Tania
T
Department of Biochemical Sciences, Center of Excellence for Scientific Research DENOTHE, Department of Anatomy, University of Florence, Italy.
Cozzi
Giacomo
G
Raugei
Giovanni
G
Formigli
Lucia
L
Ramponi
Giampietro
G
Chiarugi
Paola
P
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
D000199:Actins; D016023:Integrins; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine