A role for the myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion
A role for the myoblast city homologues Dock1 and Dock5 and the adaptor proteins Crk and Crk-like in zebrafish myoblast fusion
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DOI：
10.1242/dev.001214
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发表时间：
2007-09-01
期刊：
影响因子：
4.6
通讯作者：
Ingham, Philip W.
中科院分区：
文献类型：
--
作者：
Moore, Catherine A.;Parkin, Caroline A.;Ingham, Philip W.
成肌细胞融合遵循一个确定的事件序列，这在脊椎动物和无脊椎动物中惊人地相似。果蝇的遗传分析已经确定了许多介导融合过程中不同步骤的分子;相比之下，脊椎动物胚胎发生过程中成肌细胞融合的分子基础仍然很差。果蝇细胞内融合途径的一个关键组成部分是由成肌细胞城（mbc）基因编码的蛋白质，该基因是脊椎动物胞质分裂专用蛋白1（DOCK 1，以前称为DOCK 180）的密切同源物。使用吗啉代反义寡核苷酸介导的基因敲低在斑马鱼胚胎中的活性，我们表明，胚胎快速收缩成肌细胞的融合需要Dock 1和密切相关的Dock 5蛋白的活动。此外，我们还表明，已知Dock蛋白与其发生物理相互作用的衔接蛋白Crk和Crk样蛋白（Crkl）也是成肌细胞融合所需的。
Myoblast fusion follows a defined sequence of events that is strikingly similar in vertebrates and invertebrates. Genetic analysis in Drosophila has identified many of the molecules that mediate the different steps in the fusion process; by contrast, the molecular basis of myoblast fusion during vertebrate embryogenesis remains poorly characterised. A key component of the intracellular fusion pathway in Drosophila is the protein encoded by the myoblast city (mbc) gene, a close homologue of the vertebrate protein dedicator of cytokinesis 1 (DOCK1, formerly DOCK180). Using morpholino antisense-oligonucleotide-mediated knockdown of gene activity in the zebrafish embryo, we show that the fusion of embryonic fast-twitch myoblasts requires the activities of Dock1 and the closely related Dock5 protein. In addition, we show that the adaptor proteins Crk and Crk-like (Crkl), with which Dock proteins are known to interact physically, are also required for myoblast fusion.