Multi-functionality of dynamin family and mechanism of integrated control

我们通过Dynamin/Cortactin复合体阐明了一种新的肌动蛋白动力学调节机制。该络合物呈环状，在动力蛋白GTP水解后发生构象变化，由开环变为闭环。通过开放完形运动，复合体结合了F-肌动蛋白，稳定了肌动蛋白束。此外，我们发现N‘-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide(DBHA)as是一种动力蛋白抑制剂，可以抑制动力蛋白依赖的肌动蛋白调节。DBHA抑制动力素在迁移癌细胞系前沿的募集和褶皱的形成。对细胞的迁移、侵袭和增殖也有抑制作用。

We have clarified a novel regulatory mechanism of actin dynamics by dynamin/cortactin complex. The complex is ring-shaped and it changed the conformation upon dynamin GTP hydrolysis, from open ring to close ring. By the open-cloze motion, the complex bundled F-actins and stabilized the actin bundles. Furthermore, we identified N'-[4-(dipropylamino)benzylidene]-2-hydroxybenzohydrazide(DBHA)as a dynamin inhibitor that suppress dynamin-dependent actin regulation. DBHA inhibited recruitment of dynamin to the leading edge of migrating cancer cell line and ruffle formation. It also showed inhibitory effect in cell migration, invasion, and proliferation.