Moore Catherine A, Parkin Caroline A, Bidet Yannick, Ingham Philip W
MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Science, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Development. 2007 Sep;134(17):3145-53. doi: 10.1242/dev.001214. Epub 2007 Aug 1.
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.
成肌细胞融合遵循一系列明确的事件顺序,这在脊椎动物和无脊椎动物中惊人地相似。果蝇中的遗传分析已经鉴定出许多介导融合过程中不同步骤的分子;相比之下,脊椎动物胚胎发育过程中成肌细胞融合的分子基础仍知之甚少。果蝇细胞内融合途径的一个关键成分是成肌细胞城市(mbc)基因编码的蛋白质,它是脊椎动物胞质分裂专用蛋白1(DOCK1,原称DOCK180)的紧密同源物。利用吗啉代反义寡核苷酸介导的斑马鱼胚胎基因活性敲低,我们发现胚胎快肌成肌细胞的融合需要Dock1和密切相关的Dock5蛋白的活性。此外,我们还发现衔接蛋白Crk和类Crk(Crkl)(已知Dock蛋白与之有物理相互作用)也是成肌细胞融合所必需的。