Tures to invade surrounding tissues. Coordinated remodelling of membranes and the cytoskeleton is also required to generate membrane vesicles and transport them between different intracellular membrane trafficking compartments.Therefore, it was not surprising that Ruk/CIN85 had been previously found to be implicated in the regulation of both these processes, and majority of proteins recruited by the SH3 domains of Ruk/CIN85 identified here localise to membranes or cytoskeletal structures. Recent studies suggest that physiologically diverse cellular processes, which require integration of membranes with the adjacent cytoskeleton, including vesicle-mediated transport, cell adhesion, migration and invasion may use compatible molecular mechanisms utilising similar sets of proteins and interactions. For this reason interactions between Ruk/CIN85 and such promiscuous proteins are of particular interest. For instance, previously Ruk/CIN85 has been implicated in the interaction with Arf GTPaseactivating protein ASAP1/AMAP1, which is one of the core components of invadopodia in invasive cancer cells, and also regulates focal adhesions, circular dorsal ruffles and membrane trafficking [20,21]. Several such proteins are among the novel Ruk/CIN85 interaction candidates identified here. Two of them, N-WASP, a regulator of Arp2/3mediated actin nucleation and elongation at membranes, and Dynamin 2, a mechanoenzyme capable to promote tubulation and fission of membranes, are worth of special attention. Both these proteins act in a coordinated manner at the protrusive structures of motile cells and atPage 10 of(page number not for citation purposes)Proteome Science 2009, 7:http://www.proteomesci.com/content/7/1/Ruk/CIN85 and vesicle-mediated trafficking Our present data indicate that via the SH3 domains PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25447644 Ruk/ CIN85 may recruit a number of protein molecules required for the proper formation and function of coated vesicles. Majority of these proteins, including dynamins, Pepstatin A web inositol-5′-phosphatase synaptojanin 1 and N-WASP are recruited to coated pits at the late steps of coated vesicle formation to complete vesicle fission [34-36].present data demonstrate that the SH3 domains of Ruk/ CIN85 could bind cytoplasmic tyrosine kinase c-Abl, which had been implicated in the negative regulation of EGFR endocytosis via the impairment of c-Cbl-receptor interaction [41]. We therefore speculate that the recruitment of c-Abl by Ruk/CIN85 may serve as a mechanism to exclude some Ruk/CIN85 partners from the protein complexes, retain it (and c-Cbl) away from the plasma membrane and release for other cellular processes. It has been previously suggested that scaffolding functions of Ruk/CIN85 in membrane transport are not limited to the formation of coated vesicles, but may also extend to the regulation of subsequent vesicle trafficking events [10]. In favour of this hypothesis, the SH3 domains of Ruk/CIN85 recruit diverse proteins implicated in distinct membrane trafficking events. Some of them, such as adaptor proteins AIP1/Alix and Dab2 are the known Ruk/ CIN85 interaction partners [42,43]. Other proteins, including adaptor Vps37b, serine/threonine kinase PCTAIRE-1 or inositol-5′-phosphatase SHIP2 are the novel interaction candidates [44-46]. Intriguingly, Ruk/CIN85 itself displays several features characteristic for the components of vesicle coats. First, recruitment of Ruk/CIN85 to (the Golgi) membranes is modulated by Arf1 GTPase activity [11]. Second, Ruk/ CIN85 can rec.