Dynasore, a cell-permeable inhibitor of dynamin
Dynasore, a cell-permeable inhibitor of dynamin
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DOI：
10.1016/j.devcel.2006.04.002
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发表时间：
2006-06-01
影响因子：
11.8
通讯作者：
Kirchhausen, Tomas
中科院分区：
文献类型：
--
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
发动蛋白是网格蛋白依赖的包被囊泡形成所必需的。它是在从完全形成的凹坑到夹断囊泡的过渡期间的后期阶段膜出芽所必需的。发动蛋白也可能在囊泡形成的早期阶段发挥其他作用。我们已经筛选了大约16,000种小分子，并确定了1种在体外干扰动力蛋白1、动力蛋白2和线粒体动力蛋白Drp 1的GTP酶活性的分子，在此命名为dynasore，但不干扰其他小GTP酶。Dynasore作为内吞途径的有效抑制剂，已知依赖于发动蛋白，在Dynasore添加后数秒内快速阻断包被囊泡的形成。在dynasore处理过程中积累了两种类型的涂层凹坑中间体，U形，半形成的凹坑和O形，完全形成的凹坑，在夹断时被捕获。因此，发动蛋白在网格蛋白涂层形成过程中分两步起作用;这两步可能都需要GTP水解。
Dynamin is essential for clathrin-dependent coated vesicle formation. It is required for membrane budding at a late stage during the transition from a fully formed pit to a pinched-off vesicle. Dynamin may also fulfill other roles during earlier stages of vesicle formation. We have screened about 16,000 small molecules and have identified 1, named here dynasore, that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases. Dynasore acts as a potent inhibitor of endocytic pathways known to depend on dynamin by rapidly blocking coated vesicle formation within seconds of dynasore addition. Two types of coated pit intermediates accumulate during dynasore treatment, U-shaped, half formed pits and O-shaped, fully formed pits, captured while pinching off. Thus, dynamin acts at two steps during clathrin coat formation; GTP hydrolysis is probably needed at both steps.