Proteins of the ADF/cofilin family play a central role in the disassembly of actin filaments, and their activity must be tightly regulated in cells. Recently, the oxidation of actin filaments by the enzyme MICAL1 was found to amplify the severing action of cofilin through unclear mechanisms. Using single filament experiments in vitro, we found that actin filament oxidation by MICAL1 increases, by several orders of magnitude, both cofilin binding and severing rates, explaining the dramatic synergy between oxidation and cofilin for filament disassembly. Remarkably, we found that actin oxidation bypasses the need for cofilin activation by dephosphorylation. Indeed, non‐activated, phosphomimetic S3D‐cofilin binds and severs oxidized actin filaments rapidly, in conditions where non‐oxidized filaments are unaffected. Finally, tropomyosin Tpm1.8 loses its ability to protect filaments from cofilin severing activity when actin is oxidized by MICAL1. Together, our results show that MICAL1‐induced oxidation of actin filaments suppresses their physiological protection from the action of cofilin. We propose that, in cells, direct post‐translational modification of actin filaments by oxidation is a way to trigger their disassembly.

中文翻译：

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MICAL1 对肌动蛋白丝的氧化抑制了对 cofilin 诱导的分解的保护作用

ADF/cofilin 家族的蛋白质在肌动蛋白丝的分解中起核心作用，并且它们的活性必须在细胞中受到严格调节。最近，发现酶 MICAL1 对肌动蛋白丝的氧化通过不清楚的机制放大了 cofilin 的切断作用。在体外使用单丝实验，我们发现 MICAL1 对肌动蛋白丝的氧化增加了几个数量级，cofilin 结合和切断率，解释了氧化和 cofilin 之间在丝分解方面的显着协同作用。值得注意的是，我们发现肌动蛋白氧化通过去磷酸化绕过了 cofilin 激活的需要。实际上，在未氧化的细丝不受影响的情况下，非活化的拟磷 S3D-cofilin 会迅速结合并切断氧化的肌动蛋白细丝。最后，当肌动蛋白被 MICAL1 氧化时，原肌球蛋白 Tpm1.8 失去了保护细丝免受 cofilin 切断活性的能力。总之，我们的结果表明，MICAL1 诱导的肌动蛋白丝氧化抑制了它们对 cofilin 作用的生理保护。我们建议，在细胞中，