Redox regulation of β-actin during integrin-mediated cell adhesion
Redox regulation of β-actin during integrin-mediated cell adhesion
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DOI：
10.1074/jbc.m603040200
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发表时间：
2006-08-11
影响因子：
4.8
通讯作者：
Chiarugi, Paola
中科院分区：
文献类型：
--
作者：
Fiaschi, Tania;Cozzi, Giacomo;Chiarugi, Paola
肌动蛋白对外源性氧化应激的氧化还原敏感性最近被报道。我们在这里报告了第一个证据，在体内肌动蛋白氧化还原调节的生理来源的活性氧物种，特别是那些由整合素受体在细胞黏附产生的物种。肌动蛋白的氧化是通过半胱氨酸374和谷胱甘肽之间的混合二硫键形成的；这种修饰对于扩散和细胞骨架的组织是必不可少的。肌动蛋白谷胱甘肽基化的障碍，无论是通过GSH耗尽还是C374A氧化还原不敏感突变体的表达，都会极大地影响细胞的铺展和应激纤维的形成，导致抑制放线肌球蛋白复合体的分解。这些数据表明，肌动蛋白谷胱甘肽化是细胞扩散和细胞骨架组织所必需的，它在细胞黏附过程中对放线肌球蛋白复合体的分解起着关键作用。
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.