Identification and characterization of novel Ras plasma membrane signalling complex modulators - the RAS-NANOME. (FNR co-application)

RAS蛋白是细胞内通讯系统(信号网络)的重要成员。它们位于细胞膜的内表面，从那里它们帮助传递控制细胞是否增殖、变化或死亡的信息。小区信令网络通常被预先分组在一起，以确保其中的信息传输是有效的。RAS蛋白在细胞膜内部被组织成小簇(纳米簇)，这种组织是RAS正常功能的基本要求。已经确定了几种配对蛋白，它们能够专门针对四种不同的RAS蛋白中的一种或几种改变纳米聚集。我们将RAS-纳米簇调控蛋白质组定义为RAS-NANOME。它们是影响RAS正常和疾病相关功能的重要靶点。我们的项目旨在确定RAS-NANOME的新成员。我们将标记细胞中与RAS相邻的所有蛋白质，以确定可能的候选蛋白，然后筛选它们调节RAS纳米聚集的能力。我们将挑选例子，展示具体调控纳米集群的最佳证据，并描述它们是如何做到这一点的。这将包括确定它们如何与RAS相互作用，以及它们如何调节细胞活动。因此，我们将评估这些新的RAS-NANOME成员能够影响RAS信令网络的程度。最后，我们将结合所有新的和以前发现的RAS-NANOME成员来确定他们是合作还是竞争来调节RAS纳米聚集和信号传递，以及细胞通常经历的条件可能如何影响这一点。

Ras proteins are important members of the communication systems (signalling networks) within cells. They sit on the inner surface of cell membrane from where they help to relay information that controls whether cells will proliferate, change or die. Cell signalling networks are often pre-grouped together to ensure that information transfer within them is efficient. Ras proteins are organised into small clusters (nanoclusters) at the inside of the cell membrane and this organisation is an essential requirement for proper Ras function. Several partner proteins have been identified that are capable of changing the nanoclustering specifically for one or a few of the four different Ras proteins. We define the RAS-NANOcluster modulating proteOME as the RAS-NANOME. They represent important targets for influencing the normal and disease-associated functions of Ras. Our project aims to identify new members of the RAS-NANOME. We will label all proteins that sit next to Ras in the cell to identify likely candidates and then screen them for their ability to regulate Ras nanoclustering. We will pick examples that show the best evidence for specifically regulating nanoclustering and characterise how they do this. This will include identifying how they interact with Ras and how the cell activity is modulated by them. Thus, we will assess the extent to which these new RAS-NANOME members are able to influence Ras signalling networks. Finally, we will take a combined look at all of the new and previously identified RAS-NANOME members to determine whether they co-operate or compete to regulate Ras nanoclustering and signalling and how the conditions that cells typically experience might influence this.