Project 444933

The RAS superfamily is composed of nearly 150 proteins divided into RAS, RHO, ARF and RAB. The ARF family is composed of 30 proteins and approximately 42 regulators involved in basic cellular functions of membrane trafficking. Many of these proteins are conserved throughout evolution. These ARFs are strategically distributed in various membranes including the plasma membrane as well as more specialized intracellular membranes. The best studied ARF1 and ARF6 are controlling vesicular traffic, cargo proteins delivery, and alter the composition of membranes by recruiting various enzymes. ARFs are regulated by activators and inactivators. Once in an active state, ARFs can then engage into interactions with proteins that transmit specific signals for biological outputs. Together, the ARFs, GAPs and GEFs form a large network of over 70 proteins. While some of the ARF family members have been studied in detail, most remain poorly studied. One important challenge to gain the needed deep understanding of ARP proteins is to define how they engage into interactions with their regulators and effectors. Given that ARFs are tightly inserted into membranes, it has been quite challenging to map their interacting proteins. Here, we report the systematic mapping of the interacting partners of all ARF proteins. In this project, we aim to characterize new protein complexes that may contribute to membrane traffic in health and disease cellular models. We will deeply characterize the large amount of data that we accumulated using bioinformatics. The novel interactions will be validated using approaches including fly genetics. The molecular and biological functions of these interactions will be analyzed including via structural approaches. These studies represent the first systematic analyses of the ARF proteins and will reveal many new connections. Derailed ARF signalling leads to various diseases, hence this project will shed light on some of the basic molecular mechanisms implicated.