EML4 promotes the loading of NUDC to the spindle for mitotic progression
EML4 promotes the loading of NUDC to the spindle for mitotic progression
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DOI：
10.1080/15384101.2015.1026514
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发表时间：
2015-05-19
期刊：
影响因子：
4.3
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
--
作者：
Chen, Dan;Ito, Satoko;Senga, Takeshi
棘皮动物微管相关蛋白（EMAP）样（EML）家族蛋白是具有保守的疏水性EMAP样蛋白（HELP）结构域和多个WD 40结构域的微管相关蛋白。在这项研究中，我们研究了EML 4，这是EML家族的成员，在细胞分裂中的作用。延时显微镜分析表明，EML 4耗尽诱导染色体在中期和延迟后期启动不对齐。进一步的免疫荧光分析表明，EML 4是必需的有丝分裂纺锤体的组织和适当的附件的着丝粒微管。我们通过质谱分析寻找EML4相关蛋白，发现核分布基因C（NUDC）蛋白与EML4相关，该蛋白是有丝分裂进展的关键因素。这种相互作用由EML 4的WD 40重复序列和NUDC的C-末端介导。在缺乏EML 4的情况下，NUDC不再能够定位于有丝分裂纺锤体，而NUDC不适合EML 4定位。我们的研究结果表明，EML 4是关键的加载NUDC到有丝分裂纺锤体的有丝分裂进程。
Echinoderm microtubule-associated protein (EMAP)-like (EML) family proteins are microtubule-associated proteins that have a conserved hydrophobic EMAP-like protein (HELP) domain and multiple WD40 domains. In this study, we examined the role of EML4, which is a member of the EML family, in cell division. Time-lapse microscopy analysis demonstrated that EML4 depletion induced chromosome misalignment during metaphase and delayed anaphase initiation. Further analysis by immunofluorescence showed that EML4 was required for the organization of the mitotic spindle and for the proper attachment of kinetochores to microtubules. We searched for EML4-associating proteins by mass spectrometry analysis and found that the nuclear distribution gene C (NUDC) protein, which is a critical factor for the progression of mitosis, was associated with EML4. This interaction was mediated by the WD40 repeat of EML4 and by the C-terminus of NUDC. In the absence of EML4, NUDC was no longer able to localize to the mitotic spindle, whereas NUDC was dispensable for EML4 localization. Our results show that EML4 is critical for the loading of NUDC onto the mitotic spindle for mitotic progression.