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

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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.