SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics.
SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics.
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DOI：
10.1038/ncb2871
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发表时间：
2013-12
影响因子：
21.3
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中科院分区：
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肌动蛋白的聚合性质因其保守的蛋氨酸 (Met)-44 残基的氧化而发生显着改变。介导这种效应的是一种特定的氧化还原 (Redox) 酶 Mical，它与 Semaphorin 排斥性指导信号一起作用并选择性氧化 Met-44。我们现在发现这种肌动蛋白调节过程是可逆的。采用遗传方法，我们鉴定了一种特定的甲硫氨酸亚砜还原酶 SelR，它对抗 Mical 氧化还原活性和 Semaphorin/Plexin 排斥，以指导体内多种肌动蛋白依赖性细胞行为。 SelR特异性催化甲硫氨酸亚砜的R-异构体（甲硫氨酸-R-亚砜）还原为甲硫氨酸，我们发现SelR直接还原了Mical氧化的肌动蛋白，恢复了其正常的聚合性质。这些结果表明，Mical 立体特异性氧化肌动蛋白，生成肌动蛋白 Met-44-R-亚砜 (actinMet(R)O-44)，并且还暗示特定 Met/Met(R)O 残基的相互转化是调节蛋白质功能的精确手段。因此，我们的结果揭示了控制细胞和发育生物学的特定可逆氧化还原肌动蛋白调节系统。
Actin's polymerization properties are dramatically altered by oxidation of its conserved methionine (Met)-44 residue. Mediating this effect is a specific oxidation-reduction (Redox) enzyme, Mical, that works with Semaphorin repulsive guidance cues and selectively oxidizes Met-44. We now find that this actin regulatory process is reversible. Employing a genetic approach, we identified a specific methionine sulfoxide reductase enzyme SelR that opposes Mical Redox activity and Semaphorin/Plexin repulsion to direct multiple actin-dependent cellular behaviors in vivo. SelR specifically catalyzes the reduction of the R-isomer of methionine sulfoxide (methionine-R-sulfoxide) to methionine, and we found that SelR directly reduced Mical-oxidized actin, restoring its normal polymerization properties. These results indicate that Mical oxidizes actin stereo-specifically to generate actin Met-44-R-sulfoxide (actinMet(R)O-44) – and they also implicate the interconversion of specific Met/Met(R)O residues as a precise means to modulate protein function. Our results therefore uncover a specific reversible Redox actin regulatory system that controls cell and developmental biology.