The mechanisms regulating the disassembly of branched actin networks formed by the Arp2/3 complex still remain to be fully elucidated. In addition, the impact of Arp3 isoforms on the properties of Arp2/3 are also unexplored. We now demonstrate that Arp3 and Arp3B isocomplexes promote actin assembly equally efficiently but generate branched actin networks with different disassembly rates. Arp3B dissociates significantly faster than Arp3 from the network, and its depletion increases actin stability. This difference is due to the oxidation of Arp3B, but not Arp3, by the methionine monooxygenase MICAL2, which is recruited to the actin network by coronin 1C. Substitution of Arp3B Met293 by threonine, the corresponding residue in Arp3, increases actin network stability. Conversely, replacing Arp3 Thr293 with glutamine to mimic Met oxidation promotes disassembly. The ability of MICAL2 to enhance network disassembly also depends on cortactin. Our observations demonstrate that coronin 1C, cortactin, and MICAL2 act together to promote disassembly of branched actin networks by oxidizing Arp3B-containing Arp2/3 complexes.

中文翻译：

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MICAL2 通过氧化含有 Arp3B 的 Arp2/3 复合物来增强分支肌动蛋白网络分解


调节 Arp2/3 复合物形成的分支肌动蛋白网络分解的机制仍有待充分阐明。此外，Arp3 异构体对 Arp2/3 特性的影响也尚未被探索。我们现在证明 Arp3 和 Arp3B 同工复合物同样有效地促进肌动蛋白组装，但生成具有不同拆卸速率的分支肌动蛋白网络。 Arp3B 从网络上解离的速度明显快于 Arp3，并且其耗尽会增加肌动蛋白的稳定性。这种差异是由于甲硫氨酸单加氧酶 MICAL2 氧化了 Arp3B，而不是 Arp3，MICAL2 被 Coronin 1C 招募到肌动蛋白网络。用苏氨酸（Arp3 中的相应残基）取代 Arp3B Met293，可增加肌动蛋白网络的稳定性。相反，用谷氨酰胺替换 Arp3 Thr293 以模拟 Met 氧化会促进分解。 MICAL2增强网络分解的能力也依赖于cortactin。我们的观察表明，coronin 1C、cortactin 和 MICAL2 共同作用，通过氧化含有 Arp3B 的 Arp2/3 复合物来促进分支肌动蛋白网络的分解。