Redox Regulation of β-Actin during Integrin-mediated Cell Adhesion*
- Tania Fiaschi‡§,1,
- Giacomo Cozzi‡,1,
- Giovanni Raugeiद,
- Lucia Formigli∥,
- Giampietro Ramponiঠand
- Paola Chiarugiद,2
- ‡Department of Biochemical Sciences, ¶Center of Excellence for Scientific Research DENOTHE, ∥Department of Anatomy, University of Florence, and the §Istituto Interuniversitario di Miologia, Viale Morgagni 50, 50134 Florence, Italy
- ↵2 To whom correspondence should be addressed: Paola Chiarugi, Dipartimento di ScienzeBiochimiche, Viale Morgagni 50, 50134 Firenze, Italy. Tel.: 39-055-4598343; Fax: 39-055-4498905; E-mail: paola.chiarugi{at}unifi.it.
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.
- Received March 30, 2006.
- Revision received May 30, 2006.
- The American Society for Biochemistry and Molecular Biology, Inc.
