NuMA is required for the proper completion of mitosis.
NuMA is required for the proper completion of mitosis.
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DOI：
10.1083/jcb.120.4.947
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发表时间：
1993-02
期刊：
影响因子：
--
通讯作者：
Cleveland DW
中科院分区：
文献类型：
--
作者：
Compton DA;Cleveland DW
NuMA 是一种 236 kD 的核内蛋白，在有丝分裂期间通过与纺锤体的中心体周围结构域结合而分布到每个子细胞中。 NuMA 多肽由由不连续的 1500 个氨基酸卷曲螺旋间隔区隔开的球状头部和尾部结构域组成。尽管截短的 NuMA 适当定位于细胞核和纺锤体极，但缺乏球状头部结构域的人 NuMA 的表达导致细胞无法经历胞质分裂并在随后的间期组装多个小核（微核）。这种显性表型在形态上与 tsBN2 细胞系相同，后者在染色质结合蛋白 RCC1 中携带温度敏感突变。在限制温度下，这些细胞结束有丝分裂，但未完成胞质分裂，随后在随后的间期形成微核。我们证明野生型 NuMA 在这些突变细胞的最新有丝分裂阶段被降解，并且 NuMA 被排除在有丝分裂后组装的微核之外。通过强制表达野生型 NuMA 来提高这些突变细胞中的 NuMA 水平足以恢复单个正常大小核的有丝分裂后组装。缺乏球状尾部结构域的人 NuMA 的表达导致 NuMA 既不能靶向间期核，也不能与有丝分裂纺锤体结合。在这种突变体存在的情况下，细胞正常进行有丝分裂，但在每个子细胞中组装微核。这些发现的总和表明，NuMA 功能是有丝分裂过程中染色体分离和/或核重组末期所必需的。
NuMA is a 236-kD intranuclear protein that during mitosis is distributed into each daughter cell by association with the pericentrosomal domain of the spindle apparatus. The NuMA polypeptide consists of globular head and tail domains separated by a discontinuous 1500 amino acid coiled-coil spacer. Expression of human NuMA lacking its globular head domain results in cells that fail to undergo cytokinesis and assemble multiple small nuclei (micronuclei) in the subsequent interphase despite the appropriate localization of the truncated NuMA to both the nucleus and spindle poles. This dominant phenotype is morphologically identical to that of the tsBN2 cell line that carries a temperature-sensitive mutation in the chromatin-binding protein RCC1. At the restrictive temperature, these cells end mitosis without completing cytokinesis followed by micronucleation in the subsequent interphase. We demonstrate that the wild-type NuMA is degraded in the latest mitotic stages in these mutant cells and that NuMA is excluded from the micronuclei that assemble post-mitotically. Elevation of NuMA levels in these mutant cells by forcing the expression of wild-type NuMA is sufficient to restore post-mitotic assembly of a single normal-sized nucleus. Expression of human NuMA lacking its globular tail domain results in NuMA that fails both to target to interphase nuclei and to bind to the mitotic spindle. In the presence of this mutant, cells transit through mitosis normally, but assemble micronuclei in each daughter cell. The sum of these findings demonstrate that NuMA function is required during mitosis for the terminal phases of chromosome separation and/or nuclear reassembly.