A Drosophila overexpression screen for modifiers of Rho signalling in cytokinesis
A Drosophila overexpression screen for modifiers of Rho signalling in cytokinesis
复制标题
DOI：
10.4161/fly.3806
复制
发表时间：
2007-01-01
期刊：
影响因子：
1.2
通讯作者：
Saint, Robert
中科院分区：
文献类型：
--
作者：
Gregory, Stephen L.;Shandala, Tetyana;Saint, Robert
为了确定在胞质分裂过程中调节Rho信号的基因，我们测试了一组2190个基因的过度表达对Rho激活缺陷引起的眼睛表型的影响。由此产生的112个修饰基因座主要分为三类：细胞周期基因、信号效应器和代谢酶。我们进一步开发了一系列基因测试，将相互作用因子提炼为最有可能在胞质分裂期间改变Rho信号的相互作用因子。除了以前在胞质分裂过程中涉及Rho途径的一些基因外，我们还鉴定了四个新的主要候选基因：CDC14、Pitslre、PDK1和Thline/DIAP1。然而，在其他生物中，CDC14同源基因与胞质分裂有关，与Thread/Diap1相关的分子也是如此。发现了几个基因冗余的修饰物，突显了过度表达筛查识别传统功能丧失方法难以识别的基因的能力。因此，过度表达筛查和敏化表型可能有助于确定许多预期与胞质分裂有关但以前的基因筛查没有发现的因子。
To identify genes that modulate Rho signalling during cytokinesis we tested the effect of overexpressing a set of 2190 genes on an eye phenotype caused by defective Rho activation. The resulting 112 modifier loci fell into three main classes: cell cycle genes, signalling effectors and metabolic enzymes. We developed a further series of genetic tests to refine the interactors into those most likely to modify Rho signalling during cytokinesis. In addition to a number of genes previously implicated in the Rho pathway during cytokinesis, we identified four novel primary candidates: cdc14, Pitslre, PDK1 and thread/diap1. cdc14 orthologs have, however, been implicated in cytokinesis in other organisms, as have molecules related to Thread/Diap1. The identification of several modifiers that are genetically redundant paralogs highlights the ability of overexpression screens to identify genes that are refractory to traditional loss-of-function approaches. Overexpression screens and sensitized phenotypes, therefore, may help identify the many factors that are expected to be involved in cytokinesis but have not been discovered by previous genetic screens.