Cellular form and function - and thus normal development and physiology - are specified via proteins that control the organization and dynamic properties of the actin cytoskeleton. Using the Drosophila model, we have recently identified an unusual actin regulatory enzyme, Mical, which is directly activated by F-actin to selectively post-translationally oxidize and destabilize filaments - regulating numerous cellular behaviors. Mical proteins are also present in mammals, but their actin regulatory properties, including comparisons among different family members, remain poorly defined. We now find that each human MICAL family member, MICAL-1, MICAL-2, and MICAL-3, directly induces F-actin dismantling and controls F-actin-mediated cellular remodeling. Specifically, each human MICAL selectively associates with F-actin, which directly induces MICALs catalytic activity. We also find that each human MICAL uses an NADPH-dependent Redox activity to post-translationally oxidize actin's methionine (M) M44/M47 residues, directly dismantling filaments and limiting new polymerization. Genetic experiments also demonstrate that each human MICAL drives F-actin disassembly in vivo, reshaping cells and their membranous extensions. Our results go on to reveal that MsrB/SelR reductase enzymes counteract each MICAL's effect on F-actin in vitro and in vivo. Collectively, our results therefore define the MICALs as an important phylogenetically-conserved family of catalytically-acting F-actin disassembly factors.

中文翻译：

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MICALs是从果蝇到人类保守的F-肌动蛋白消除氧化还原酶的家族。

细胞形式和功能-以及因此的正常发育和生理-通过控制肌动蛋白细胞骨架组织和动态特性的蛋白质来确定。使用果蝇模型，我们最近发现了一种异常的肌动蛋白调节酶Mical，该酶被F-肌动蛋白直接激活以选择性地翻译后氧化和破坏细丝，从而调节多种细胞行为。哺乳动物中也存在蛋白质，但是它们的肌动蛋白调节特性（包括不同家族成员之间的比较）仍然不清楚。现在，我们发现每个人类MICAL家庭成员MICAL-1，MICAL-2和MICAL-3直接诱导F-肌动蛋白拆卸并控制F-肌动蛋白介导的细胞重塑。具体而言，每个人MICAL选择性地与F-肌动蛋白结合，它直接诱导了MICALs的催化活性。我们还发现，每个人的MICAL都使用NADPH依赖性的Redox活性来翻译后氧化肌动蛋白的蛋氨酸（M）M44 / M47残基，直接拆解细丝并限制了新的聚合反应。遗传实验还表明，每个人MICAL都会驱动F-肌动蛋白在体内分解，重塑细胞及其膜状延伸。我们的研究结果继续表明，MsrB / SelR还原酶可以抵消每种MICAL在体外和体内对F-肌动蛋白的作用。总的来说，我们的结果因此将MICALs定义为重要的系统发育保守的F-actin分解因子。s的蛋氨酸（M）M44 / M47残留物，可直接拆卸长丝并限制新的聚合反应。遗传实验还表明，每个人MICAL都会驱动F-肌动蛋白在体内分解，重塑细胞及其膜状延伸。我们的结果继续揭示，MsrB / SelR还原酶在体内外均能抵消每种MICAL对F-肌动蛋白的作用。总的来说，我们的结果因此将MICALs定义为重要的系统发育保守的F-actin分解因子。s的蛋氨酸（M）M44 / M47残留物，可直接拆卸长丝并限制新的聚合反应。遗传实验还表明，每个人MICAL都会驱动F-肌动蛋白在体内分解，重塑细胞及其膜状延伸。我们的结果继续揭示，MsrB / SelR还原酶在体内外均能抵消每种MICAL对F-肌动蛋白的作用。总的来说，我们的结果因此将MICALs定义为重要的系统发育保守的F-actin分解因子。在体外和体内对F-肌动蛋白的作用。总的来说，我们的结果因此将MICALs定义为重要的系统发育保守的F-actin分解因子。在体外和体内对F-肌动蛋白的作用。总的来说，我们的结果因此将MICALs定义为重要的系统发育保守的F-actin分解因子。