动力蛋白小分子抑制剂dynasore在胞吞作用调控中的应用。
Use of dynasore, the small molecule inhibitor of dynamin, in the regulation of endocytosis.
作者信息
Kirchhausen Tom, Macia Eric, Pelish Henry E
机构信息
Department of Cell Biology, Harvard Medical School, and IDI Immune Research Institute, Boston, Massachusetts, USA.
出版信息
Methods Enzymol. 2008;438:77-93. doi: 10.1016/S0076-6879(07)38006-3.
Abstract
The large GTPase dynamin is essential for clathrin-dependent coated-vesicle formation. Dynasore is a cell-permeable small molecule that inhibits the GTPase activity of dynamin1, dynamin2 and Drp1, the mitochondrial dynamin. Dynasore was discovered in a screen of approximately 16,000 compounds for inhibitors of the dynamin2 GTPase. Dynasore is a noncompetitive inhibitor of dynamin GTPase activity and blocks dynamin-dependent endocytosis in cells, including neurons. It is fast acting (seconds) and its inhibitory effect in cells can be reversed by washout. Here we present a detailed synthesis protocol for dynasore, and describe a series of experiments used to analyze the inhibitory effects of dynasore on dynamin in vitro and to study the effects of dynasore on endocytosis in cells.
摘要
大型GTP酶发动蛋白对于网格蛋白依赖的包被小泡形成至关重要。动力蛋白抑制剂是一种可透过细胞的小分子，它能抑制发动蛋白1、发动蛋白2以及线粒体发动蛋白Drp1的GTP酶活性。动力蛋白抑制剂是在对约16000种化合物进行筛选以寻找发动蛋白2 GTP酶抑制剂时发现的。动力蛋白抑制剂是发动蛋白GTP酶活性的非竞争性抑制剂，可阻断细胞（包括神经元）中依赖发动蛋白的内吞作用。它起效迅速（数秒），且通过洗脱可逆转其在细胞中的抑制作用。在此，我们给出了动力蛋白抑制剂的详细合成方案，并描述了一系列用于分析动力蛋白抑制剂在体外对发动蛋白的抑制作用以及研究动力蛋白抑制剂对细胞内吞作用影响的实验。
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