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

神经细胞生长锥从其前缘突出丝状伪足，其动力学与轴突的延伸和寻路有关。在丝状伪足内部是F-肌动蛋白束，其尖端区域具有倒刺（或第一生长）末端，基部区域具有尖的（或缓慢生长的）末端。然而，丝状伪足动力学的精确机制仍不清楚。fascin是丝状伪足中的一种肌动蛋白成束蛋白，敲除fascin可导致培养神经元丝状伪足的缺失，表明fascin是形成肌动蛋白束的关键因素。在此，我们发现在离体条件下，F-actin被fascin捆绑的方向与丝状伪足中的方向相同。此外，肌成束蛋白/肌动蛋白束可以顺利地滑动速度为单独的F-肌动蛋白的肌球蛋白II和肌球蛋白V。在较高浓度的肌球蛋白，肌成束蛋白/肌动蛋白束解体的尖端，动力学非常相似，在体内观察到。由于肌球蛋白II和肌球蛋白V定位于丝状伪足，我们的研究结果表明，这些蛋白质可能会驱动丝状伪足肌动蛋白束向后，并导致丝状伪足基底区的解体。

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.