Rohn Jennifer L, Patel Jigna V, Neumann Beate, Bulkescher Jutta, Mchedlishvili Nunu, McMullan Rachel C, Quintero Omar A, Ellenberg Jan, Baum Buzz
Centre for Clinical Science and Technology, Division of Medicine, University College London, Wolfson House, London NW1 2HE, UK.
MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK.
Curr Biol. 2014 Nov 3;24(21):2598-605. doi: 10.1016/j.cub.2014.09.045. Epub 2014 Oct 23.
During animal cell division, an actin-based ring cleaves the cell into two. Problems with this process can cause chromosome missegregation and defects in cytoplasmic inheritance and the partitioning of organelles, which in turn are associated with human diseases. Although much is known about how chromosome segregation is coupled to cell division, the way organelles coordinate their inheritance during partitioning to daughter cells is less well understood. Here, using a high-content live-imaging small interfering RNA screen, we identify Myosin-XIX (Myo19) as a novel regulator of cell division. Previously, this actin-based motor was shown to control the interphase movement of mitochondria. Our analysis shows that Myo19 is indeed localized to mitochondria and that its silencing leads to defects in the distribution of mitochondria within cells and in mitochondrial partitioning at division. Furthermore, many Myo19 RNAi cells undergo stochastic division failure--a phenotype that can be mimicked using a treatment that blocks mitochondrial fission and rescued by decreasing mitochondrial fusion, implying that mitochondria can physically interfere with cytokinesis. Strikingly, using live imaging we also observe the inappropriate movement of mitochondria to the poles of spindles in cells depleted for Myo19 as they enter anaphase. Since this phenocopies the results of an acute loss of actin filaments in anaphase, these data support a model whereby the Myo19 actin-based motor helps to control mitochondrial movement to ensure their faithful segregation during division. The presence of DNA within mitochondria makes their inheritance an especially important aspect of symmetrical cell division.
在动物细胞分裂过程中，基于肌动蛋白的环将细胞一分为二。这一过程出现问题会导致染色体错分离以及细胞质遗传和细胞器分配方面的缺陷，进而与人类疾病相关。尽管人们对染色体分离如何与细胞分裂耦合了解颇多，但细胞器在向子细胞分配过程中如何协调其遗传的方式却知之甚少。在此，我们通过高内涵实时成像小干扰RNA筛选，鉴定出肌球蛋白-XIX（Myo19）是细胞分裂的一种新型调节因子。此前，这种基于肌动蛋白的马达蛋白已被证明可控制线粒体的间期运动。我们的分析表明，Myo19确实定位于线粒体，其沉默会导致细胞内线粒体分布以及分裂时线粒体分配出现缺陷。此外，许多Myo19 RNA干扰细胞会发生随机分裂失败——这种表型可通过阻断线粒体分裂的处理来模拟，并可通过减少线粒体融合来挽救，这意味着线粒体可能会在物理上干扰胞质分裂。引人注目的是，通过实时成像我们还观察到，在进入后期时，耗尽Myo19的细胞中线粒体向纺锤体两极出现不适当的移动。由于这一现象与后期肌动蛋白丝急性缺失的结果相似，这些数据支持了一个模型，即基于Myo19肌动蛋白的马达蛋白有助于控制线粒体运动，以确保其在分裂过程中准确分离。线粒体中DNA的存在使其遗传成为对称细胞分裂的一个特别重要的方面。
