Mitotic progression is orchestrated by the microtubule-based motor dynein, which sustains all mitotic spindle functions. During cell division, cytoplasmic dynein acts with the high-molecular-weight complex dynactin and nuclear mitotic apparatus (NuMA) to organize and position the spindle. Here, we analyze the interaction interface between NuMA and the light intermediate chain (LIC) of eukaryotic dynein. Structural studies show that NuMA contains a hook domain contacting directly LIC1 and LIC2 chains through a conserved hydrophobic patch shared among other Hook adaptors. In addition, we identify a LIC-binding motif within the coiled-coil region of NuMA that is homologous to CC1-boxes. Analysis of mitotic cells revealed that both LIC-binding sites of NuMA are essential for correct spindle placement and cell division. Collectively, our evidence depicts NuMA as the dynein-activating adaptor acting in the mitotic processes of spindle organization and positioning.

基于微管的运动动力蛋白可控制有丝分裂的进程，该动力蛋白可维持所有的有丝分裂纺锤体功能。在细胞分裂过程中，细胞质动力蛋白与高分子复合动力蛋白和核有丝分裂器（NuMA）共同组织并定位纺锤体。在这里，我们分析了NuMA和真核动力蛋白的轻中间链（LIC）之间的相互作用界面。结构研究表明，NuMA包含一个通过其他Hook衔接子共享的保守疏水补丁直接与LIC1和LIC2链接触的钩结构域。另外，我们在NuMA的螺旋线圈区域内发现了一个与CC1-box同源的LIC结合基序。对有丝分裂细胞的分析表明，NuMA的两个LIC结合位点对于正确的纺锤体放置和细胞分裂都是必不可少的。总的来说，