Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex.
Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex.
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DOI：
10.1091/mbc.e14-05-0975
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发表时间：
2014-09-15
影响因子：
3.3
通讯作者：
Cande WZ
中科院分区：
文献类型：
--
作者：
Vicente JJ;Cande WZ
病原体贾第鞭毛虫缺乏后期促进复合体/细胞周期体，但仍然能够使用少量与其他真核细胞中同源的有丝分裂检查点复合体蛋白来调节中期到后期的转变。贾第虫可能具有一个更简单和更古老的系统来调节染色体分离和有丝分裂纺锤体行为。双核病原体贾第鞭毛虫是一种高度分化的真核生物，具有半开放的有丝分裂，缺乏后期促进复合物/细胞周期体（APC/C）和许多有丝分裂检查点复合物（MCC）蛋白。然而，贾第虫有一些MCC组分（Bub 3，Mad 2和Mps 1）和来自粘附素系统的蛋白质（Smc 1和Smc 3）。Mad 2定位于细胞质，但Bub 3和Mps 1位于染色体上或细胞质中，这取决于细胞周期阶段。Bub 3，Mad 2或Mps 1的缺失导致有丝分裂指数降低，染色体分离错误（包括落后染色体）和纺锤体形态异常。在间期，MCC敲除细胞具有异常数量的细胞核，或者通常在细胞的左手侧的一个细胞核，或者具有一个错误定位的两个细胞核。这些结果表明，在贾第虫MCC蛋白的最小集发挥了重要作用，在调节有丝分裂的许多方面，包括染色体分离，两个核之间的有丝分裂的协调，以及随后的核定位。MCC蛋白在缺乏其典型靶点APC/C的生物体中的至关重要性表明这些蛋白质具有更广泛的作用，并暗示了有待发现的新途径。
The pathogen Giardia intestinalis lacks anaphase-promoting complex/cyclosome but is still able to regulate the metaphase to anaphase transition using a small number of mitotic checkpoint complex proteins homologous to those in other eukaryotic cells. Giardia may possess a simpler and more ancient system to regulate chromosome segregation and mitotic spindle behavior. The binucleate pathogen Giardia intestinalis is a highly divergent eukaryote with a semiopen mitosis, lacking an anaphase-promoting complex/cyclosome (APC/C) and many of the mitotic checkpoint complex (MCC) proteins. However, Giardia has some MCC components (Bub3, Mad2, and Mps1) and proteins from the cohesin system (Smc1 and Smc3). Mad2 localizes to the cytoplasm, but Bub3 and Mps1 are either located on chromosomes or in the cytoplasm, depending on the cell cycle stage. Depletion of Bub3, Mad2, or Mps1 resulted in a lowered mitotic index, errors in chromosome segregation (including lagging chromosomes), and abnormalities in spindle morphology. During interphase, MCC knockdown cells have an abnormal number of nuclei, either one nucleus usually on the left-hand side of the cell or two nuclei with one mislocalized. These results suggest that the minimal set of MCC proteins in Giardia play a major role in regulating many aspects of mitosis, including chromosome segregation, coordination of mitosis between the two nuclei, and subsequent nuclear positioning. The critical importance of MCC proteins in an organism that lacks their canonical target, the APC/C, suggests a broader role for these proteins and hints at new pathways to be discovered.