The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans.
The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans.
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Micals是从果蝇到人类保守的F-肌动蛋白拆除氧化还原酶的家族。
DOI：
10.1038/s41598-017-17943-5
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Terman JR
中科院分区：
文献类型：
--
作者：
Wu H;Yesilyurt HG;Yoon J;Terman JR
细胞的形态和功能--以及正常的发育和生理学--是通过控制肌动蛋白细胞骨架的组织和动态特性的蛋白质来指定的。使用果蝇模型，我们最近发现了一种不寻常的肌动蛋白调节酶，Mical，它直接被F-肌动蛋白激活，选择性地氧化和破坏细丝的稳定性-调节许多细胞行为。Mical蛋白也存在于哺乳动物中，但它们的肌动蛋白调节特性，包括不同家族成员之间的比较，仍然很难确定。我们现在发现，每个人MICAL家族成员，MICAL-1，MICAL-2和MICAL-3，直接诱导F-肌动蛋白拆除和控制F-肌动蛋白介导的细胞重塑。具体地，每个人MICAL选择性地与F-肌动蛋白结合，其直接诱导MICAL催化活性。我们还发现，每个人MICAL使用NADPH依赖性氧化还原活性来后分解氧化肌动蛋白的甲硫氨酸（M）M44/M47残基，直接分解细丝并限制新的聚合。遗传实验还表明，每个人类MICAL驱动体内F-肌动蛋白分解，重塑细胞及其膜延伸。我们的研究结果继续揭示，MSRB/SelR还原酶抵消每个MICAL的影响，在体外和体内的F-肌动蛋白。总的来说，我们的研究结果，因此定义的MICALs作为一个重要的非遗传保守的家庭催化作用的F-肌动蛋白解体因子。
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.
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影响因子：
4.5
作者：
Bachmann-Gagescu R;Dona M;Hetterschijt L;Tonnaer E;Peters T;de Vrieze E;Mans DA;van Beersum SE;Phelps IG;Arts HH;Keunen JE;Ueffing M;Roepman R;Boldt K;Doherty D;Moens CB;Neuhauss SC;Kremer H;van Wijk E
通讯作者：
van Wijk E
影响因子：
4.6
作者：
Alqassim SS;Urquiza M;Borgnia E;Nagib M;Amzel LM;Bianchet MA
通讯作者：
Bianchet MA
影响因子：
7.2
作者：
Bashaw, Greg J.;Klein, Ruediger
通讯作者：
Klein, Ruediger
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1007/978-1-4939-6448-2_1
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Alto LT;Terman JR
通讯作者：
Terman JR