Dynamics of nerve cell growth cone : Role of actin binding protein.

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Growth cone of developing nerve cell projects filopodia from their leading edge, and their dynamics have been implicated in elongation and pathfinding of axon. Inside filopodia are the bundles of F-actin with barbed (or first growing) ends in its tip region, and pointed (or slow growing) ends in the basal region. Precise mechanism of the dynamics of filopodia, however, is still unclear. Knockout of fascin, an actin bundling protein in filopodia, caused the loss of filopodia in cultured neuron, suggesting that fascin is a key player to form actin bundles. Here, we showed that orientation of F-actin bundled by fascin in vitro were the same as those in filopodium. Furthermore, fascin/actin bundles could slide smoothly as fast as individual F-actin on myosin II and myosin V.At higher concentration of myosins, fascin/actin bundles disassemble from the pointed end, the dynamics quite similar to that observed in vivo. Because myosin II and myosin V localize in filopodia, our results suggest that these proteins may drive the filopodial actin bundles backward, and cause the disassembly at basal region of filopodia.