MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, England, UK.
J Cell Biol. 2011 Sep 5;194(5):789-805. doi: 10.1083/jcb.201103168.
Although a large number of actin-binding proteins and their regulators have been identified through classical approaches, gaps in our knowledge remain. Here, we used genome-wide RNA interference as a systematic method to define metazoan actin regulators based on visual phenotype. Using comparative screens in cultured Drosophila and human cells, we generated phenotypic profiles for annotated actin regulators together with proteins bearing predicted actin-binding domains. These phenotypic clusters for the known metazoan "actinome" were used to identify putative new core actin regulators, together with a number of genes with conserved but poorly studied roles in the regulation of the actin cytoskeleton, several of which we studied in detail. This work suggests that although our search for new components of the core actin machinery is nearing saturation, regulation at the level of nuclear actin export, RNA splicing, ubiquitination, and other upstream processes remains an important but unexplored frontier of actin biology.
虽然通过经典方法已经鉴定了大量的肌动蛋白结合蛋白及其调节剂，但我们的知识仍然存在空白。在这里，我们使用全基因组 RNA 干扰作为一种系统方法，基于视觉表型来定义后生动物的肌动蛋白调节剂。通过在培养的果蝇和人细胞中的比较筛选，我们为注释的肌动蛋白调节剂以及具有预测肌动蛋白结合结构域的蛋白质生成了表型图谱。这些已知后生动物“肌动蛋白组”的表型聚类用于鉴定潜在的新核心肌动蛋白调节剂，以及一些在肌动蛋白细胞骨架调节中具有保守但研究甚少的作用的基因，其中一些我们进行了详细研究。这项工作表明，尽管我们对核心肌动蛋白机器的新组件的搜索已接近饱和，但在核肌动蛋白输出、RNA 剪接、泛素化和其他上游过程的水平上进行调节仍然是肌动蛋白生物学一个重要但尚未探索的前沿领域。
