Children's Medical Research Institute, The University of Sydney, 214 Hawkesbury Road, Westmead, NSW, 2145, Australia.
Traffic. 2012 Dec;13(12):1628-41. doi: 10.1111/tra.12001. Epub 2012 Sep 7.
A few proteins required for clathrin-mediated endocytosis (CME) are associated with successful completion of mitosis at distinct mitotic stages. Clathrin heavy chain (CHC) and epsin are required for chromosome segregation independent of their CME function and dynamin II (dynII) functions in the abscission stage of cytokinesis. In this study we screened for mitotic roles of eight CME proteins: CHC, α-adaptin, CALM, epsin, eps15, endophilin II (edpnII), syndapin II (sdpnII) and the GTPase dynII using a small interfering RNA targeting approach. All proteins, except for CALM, are associated with completion of the abscission stage of cytokinesis, suggesting that they function in this process in an endocytic-dependent manner. In support of this concept, overexpression of epsin(S357D), which blocks endocytosis, induced multinucleation. Moreover, six of them have a secondary role at earlier mitotic stages that is not dependent on their endocytic function: CHC, epsin and eps15 in chromosome segregation, and sdpnII, α-adaptin and CALM have a role in furrow ingression. Therefore, the role of endocytic proteins in mitosis is much broader than previously recognized.
几种参与网格蛋白介导的内吞作用(CME)的蛋白质与有丝分裂各阶段的成功完成有关。网格蛋白重链(CHC)和衔接蛋白在有丝分裂中的细胞分裂阶段与 CME 功能和动力蛋白 II(dynII)的功能无关,是染色体分离所必需的。在这项研究中,我们使用针对 8 种 CME 蛋白(CHC、α-衔接蛋白、CALM、衔接蛋白、eps15、内收蛋白 II(edpnII)、衔接蛋白 II(sdpnII)和 GTPase dynII)的小干扰 RNA 靶向方法筛选有丝分裂作用。除了 CALM 之外,所有蛋白质都与细胞分裂的后期胞质分裂完成有关,这表明它们以依赖内吞的方式在这个过程中发挥作用。这一概念得到了支持,epsin(S357D)的过表达阻止了内吞作用,导致多核化。此外,其中有 6 种在早期有丝分裂阶段具有次要作用,而不依赖于它们的内吞作用:CHC、epsin 和 eps15 在染色体分离中,sdpnII、α-衔接蛋白和 CALM 在沟道入侵中具有作用。因此,内吞蛋白在有丝分裂中的作用比以前认识到的要广泛得多。