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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The Atypical Rac Activator Dock 180 (dock1) Regulates Myoblast Fusion In Vivo
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The Atypical Rac Activator Dock 180 (dock1) Regulates Myoblast Fusion In Vivo

机译:非典型Rac激活物Dock 180(dock1)调节成肌细胞融合。

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Dock1 (also known as Dock180) is a prototypical member of a new family of atypical Rho GTPase activators. Genetic studies in Dro-sophila and Caenorhabditis elegans have demonstrated that Dock1 orthologues in these organisms have a crucial role in activating Rac GTPase signaling. We generated mutant alleles of the closely related Dock1 and Dock5 genes to study their function in mammals. We report that while Docks is dispensable for normal mouse embryogenesis, Dock1 has an essential role in embryonic development. A dramatic reduction of all skeletal muscle tissues is observed in Dock1-null embryos. Mechanistically, this embryonic defect is attributed to a strong deficiency in myoblast fusion, which is detectable both in vitro and in vivo. Furthermore, we have uncovered a contribution of Dock5 toward myofiber development. These studies identify Dock1 and Dock5 as critical regulators of the fusion step during primary myogenesis in mammals and demonstrate that a specific component of the myoblast fusion machinery identified in Drosophila plays an evolutionary conserved role in higher vertebrates.
机译:Dock1(也称为Dock180)是非典型Rho GTPase激活剂新家族的原型成员。对果蝇和秀丽隐杆线虫的遗传研究表明,这些生物中的Dock1直向同源物在激活Rac GTPase信号传导中起关键作用。我们生成了密切相关的Dock1和Dock5基因的突变等位基因,以研究它们在哺乳动物中的功能。我们报告,虽然码头是必不可少的正常小鼠胚胎发生,但Dock1在胚胎发育中具有重要作用。在Dock1无效的胚胎中观察到所有骨骼肌组织的急剧减少。从机理上讲,这种胚胎缺陷归因于成肌细胞融合的强烈缺陷,这在体外和体内均可检测到。此外,我们发现了Dock5对肌纤维发育的贡献。这些研究确定了Dock1和Dock5是哺乳动物原代成肌过程中融合步骤的关键调控因子,并证明在果蝇中鉴定的成肌细胞融合机制的特定组成部分在高等脊椎动物中起进化保守作用。

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