Sengar A S, Wang W, Bishay J, Cohen S, Egan S E
Programs of Cancer and Blood Research, and Developmental Biology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.
EMBO J. 1999 Mar 1;18(5):1159-71. doi: 10.1093/emboj/18.5.1159.
Clathrin-mediated endocytosis is a multistep process which requires interaction between a number of conserved proteins. We have cloned two mammalian genes which code for a number of endocytic adaptor proteins. Two of these proteins, termed Ese1 and Ese2, contain two N-terminal EH domains, a central coiled-coil domain and five C-terminal SH3 domains. Ese1 is constitutively associated with Eps15 proteins to form a complex with at least 14 protein-protein interaction surfaces. Yeast two-hybrid assays have revealed that Ese1 EH and SH3 domains bind epsin family proteins and dynamin, respectively. Overexpression of Ese1 is sufficient to block clathrin-mediated endocytosis in cultured cells, presumably through disruption of higher order protein complexes, which are assembled on the endogenous Ese1-Eps15 scaffold. The Ese1-Eps15 scaffold therefore links dynamin, epsin and other endocytic pathway components.
网格蛋白介导的内吞作用是一个多步骤过程，需要多种保守蛋白之间相互作用。我们克隆了两个哺乳动物基因，它们编码多种内吞衔接蛋白。其中两种蛋白，即Ese1和Ese2，含有两个N端EH结构域、一个中央卷曲螺旋结构域和五个C端SH3结构域。Ese1与Eps15蛋白组成型结合，形成一个具有至少14个蛋白质-蛋白质相互作用表面的复合物。酵母双杂交试验表明，Ese1的EH结构域和SH3结构域分别与epsin家族蛋白和发动蛋白结合。Ese1的过表达足以阻断培养细胞中网格蛋白介导的内吞作用，推测是通过破坏在内源性Ese1-Eps15支架上组装的高阶蛋白复合物来实现的。因此，Ese1-Eps15支架将发动蛋白、epsin和其他内吞途径成分联系起来。
