Characterization of the molecular interplay between VASP, formins and their accessory proteins during filopodium formation

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Analysis of Dictyostelium formins showed that one of the regulated formins, dDia2, is specifically involved in the formation and maintenance of filopodia. These finger-like, highly dynamic cytoskeletal structures contain bundles of linear actin filaments and seem to be used by many cell types as sensing organs to explore environmental cues. Filopodia have also been implicated in cell motility as well as in cell-substrate adhesion, however, the molecular mechanisms underlying filopodia formation are still poorly understood. Our results clearly differ from published models of filopodia formation, which suggest that the Arp2/3 complex together with VASP play key roles during this process. Our data provide conclusive evidence for an alternative model in which the nucleating and uncapping activities of a formin and the bundling activity of VASP are required. The objective of this project is the detailed characterization of Diaphanous-related formin dDia2 and its accessory proteins in order to better understand the fundamental principles and mechanisms of filopodia formation at the molecular level shared across many species.