An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphorin 3E-PlexinD1 signaling.
An image-based RNAi screen identifies SH3BP1 as a key effector of Semaphorin 3E-PlexinD1 signaling.
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DOI：
10.1083/jcb.201309004
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发表时间：
2014-05-26
期刊：
影响因子：
--
通讯作者：
Gu C
中科院分区：
文献类型：
--
作者：
Tata A;Stoppel DC;Hong S;Ben-Zvi A;Xie T;Gu C
RhoGAP蛋白SH3BP1通过与PlexinD1的相互作用和对rac1活性的调节来介导Sema3E诱导的细胞崩溃。细胞外信号必须被精确地解释在细胞内，并被转化为不同的细胞行为，通常是由细胞骨架的变化所介导的。信号素是最大的引导线索家族之一，在许多系统中发挥着关键作用。然而，不同类型的细胞如何将细胞外信号素结合转化为细胞内信号仍不清楚。在这里，我们开发并执行了一种新的基于图像的全基因组功能RNAi筛选，以寻找下游信号分子，将Semaphorin 3E(Sema3E)和PlexinD1之间的相互作用转化为细胞行为。在这个筛选中发现的基因之一是RhoGAP蛋白，SH3结构域结合蛋白1(SH3BP1)。我们证明SH3BP1通过与PlexinD1的相互作用和调节RAS相关的C3肉毒毒素底物1(Rac1)的活性来介导Sema3E诱导的细胞崩溃。SH3BP1作为Sema3E-PlexinD1的一个新的下游效应因子的发现和鉴定为解释细胞外信号如何转化为细胞骨架的变化和独特的细胞行为提供了解释，也为从我们的屏幕上鉴定其他基因以获得更完整的Plexin信号图谱奠定了基础。
The RhoGAP protein SH3BP1 mediates Sema3E-induced cell collapse through interaction with PlexinD1 and regulation of Rac1 activity. Extracellular signals have to be precisely interpreted intracellularly and translated into diverse cellular behaviors often mediated by cytoskeletal changes. Semaphorins are one of the largest families of guidance cues and play a critical role in many systems. However, how different cell types translate extracellular semaphorin binding into intracellular signaling remains unclear. Here we developed and performed a novel image-based genome-wide functional RNAi screen for downstream signaling molecules that convert the interaction between Semaphorin 3E (Sema3E) and PlexinD1 into cellular behaviors. One of the genes identified in this screen is a RhoGAP protein, SH3-domain binding protein 1 (SH3BP1). We demonstrate that SH3BP1 mediates Sema3E-induced cell collapse through interaction with PlexinD1 and regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1) activity. The identification and characterization of SH3BP1 as a novel downstream effector of Sema3E-PlexinD1 provides an explanation for how extracellular signals are translated into cytoskeletal changes and unique cell behavior, but also lays the foundation for characterizing other genes identified from our screen to obtain a more complete picture of plexin signaling.
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