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Role of Myosin-X in filopodia elongation and axon guidance

Final Activity Report Summary - MYO10 (Role of Myosin-X in filopodia elongation and axon guidance)

Migrating cells often probe their environment using thin extensions called filopodia. The way filopodia sense other molecules in their immediate surrounding and the way they relay this information to the cell to allow appropriate response to its environment is not clear despite decades of research. Recently Myosin-X has been shown to specifically localize at the tip of filopodia. Myosin-X is a member of a family of proteins called Myosins known to shuttle other molecules within the cell and thus allow their localization at the place where they are required. It is thus possible that Myosin-X shuttles molecules from the tip to the centre of the cell thus un-abling filopodia to communicate with the rest of the cell about what is detected in its environment.

To elucidate the role Myosin-X plays in filopodia, we have started a study of its movements within filopodia in relation to other molecules or to small vesicles. We have found that it is unlikely that Myosin-X interacts with vesicules within filopodia. We have also found that Myosin-X accumulated at filopodia tips is aggregated in a complex which, upon some yet unknown trigger, flows back towards the center of the cell. Attachment of Myosin-X to filaments of a molecule called actin which forms a sort of conveying belt within filopodia, is necessary for the movement of Myosin-X complexes towards the cell centre but this movement is strongly regulated by the part of Myosin-X which does not attach to actin but instead binds other molecules. The presence of Myosin-X at filopodia tips is strongly correlated to the attachment of filopodia to its surrounding, potentially helping filopodia communicate with their environment and helping the cells to migrate. The process of cell migration is at the core of many important processes in biology like cancer spreading, embryonic development, nerve growth and regeneration, immunity…