Tikhonenko Irina, Nag Dilip K, Robinson Douglas N, Koonce Michael P
Division of Translational Medicine, Wadsworth Center, Albany, NY 12201-0509, USA.
Eukaryot Cell. 2009 May;8(5):723-31. doi: 10.1128/EC.00018-09. Epub 2009 Mar 13.
Kinesins are a diverse superfamily of motor proteins that drive organelles and other microtubule-based movements in eukaryotic cells. These motors play important roles in multiple events during both interphase and cell division. Dictyostelium discoideum contains 13 kinesin motors, 12 of which are grouped into nine families, plus one orphan. Functions for 11 of the 13 motors have been previously investigated; we address here the activities of the two remaining kinesins, both isoforms with central motor domains. Kif6 (of the kinesin-13 family) appears to be essential for cell viability. The partial knockdown of Kif6 with RNA interference generates mitotic defects (lagging chromosomes and aberrant spindle assemblies) that are consistent with kinesin-13 disruptions in other organisms. However, the orphan motor Kif9 participates in a completely novel kinesin activity, one that maintains a connection between the microtubule-organizing center (MTOC) and nucleus during interphase. kif9 null cell growth is impaired, and the MTOC appears to disconnect from its normally tight nuclear linkage. Mitotic spindles elongate in a normal fashion in kif9(-) cells, but we hypothesize that this kinesin is important for positioning the MTOC into the nuclear envelope during prophase. This function would be significant for the early steps of cell division and also may play a role in regulating centrosome replication.
驱动蛋白是一个多样的运动蛋白超家族,可驱动真核细胞中的细胞器及其他基于微管的运动。这些运动蛋白在间期和细胞分裂的多个过程中发挥重要作用。盘基网柄菌含有13种驱动蛋白,其中12种可归为9个家族,外加1种孤立蛋白。此前已对13种驱动蛋白中的11种的功能进行了研究;我们在此研究剩余的两种驱动蛋白的活性,这两种都是具有中央运动结构域的亚型。驱动蛋白-13家族的Kif6似乎对细胞活力至关重要。用RNA干扰对Kif6进行部分敲低会产生有丝分裂缺陷(滞后染色体和异常纺锤体组装),这与其他生物体中驱动蛋白-13的破坏情况一致。然而,孤立的驱动蛋白Kif9参与了一种全新的驱动蛋白活性,即在间期维持微管组织中心(MTOC)与细胞核之间的连接。Kif9基因缺失的细胞生长受损,且MTOC似乎与其正常紧密的核连接断开。在Kif9(-)细胞中,有丝分裂纺锤体以正常方式延长,但我们推测这种驱动蛋白对于在前期将MTOC定位到核膜中很重要。该功能对于细胞分裂的早期步骤具有重要意义,并且可能在调节中心体复制中发挥作用。