Multi-functionality of dynamin family and mechanism of integrated control

我们已经阐明了一种新的肌动蛋白/接触复合物对肌动蛋白动力学的调节机制。该配合物呈环状，在动力蛋白GTP水解过程中构象由开环变为闭环。复合物通过开闭运动捆绑肌动蛋白并稳定肌动蛋白束。此外，我们发现N'-[4-（二丙基氨基）苄基]-2-羟基苯并肼（DBHA）是一种抑制动力蛋白依赖性肌动蛋白调节的动力蛋白抑制剂。DBHA抑制肿瘤细胞系迁移前沿的动力蛋白募集和褶边的形成。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.