A Cell Cycle Timer for Asymmetric Spindle Positioning
A Cell Cycle Timer for Asymmetric Spindle Positioning
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DOI：
10.1371/journal.pbio.1000088
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发表时间：
2009-04-01
期刊：
影响因子：
9.8
通讯作者：
Goldstein, Bob
中科院分区：
文献类型：
--
作者：
Campbell, Erin K. McCarthy;Werts, Adam D.;Goldstein, Bob
有丝分裂纺锤体向细胞一侧的移动对于许多细胞的不平等分裂是很重要的。虽然最近的进展已经开始揭示有丝分裂纺锤体移位的一些分子机制，但关于纺锤体移位是如何准确计时的还知之甚少。一种保守的有丝分裂进程机制是已知的在分裂细胞中计时的事件，尽管这从未与纺锤体移位联系在一起。该机制涉及后期促进复合体(APC)、其激活剂CDC20/Fizzy、其降解靶标细胞周期蛋白(Cyclin)和细胞周期蛋白依赖性蛋白激酶(CDK)。在这里，我们展示了这些组件包括一个以前未被识别的主轴位移计时器。在秀丽线虫受精卵中，有丝分裂纺锤体的移位是在染色体向中期板运动后不久的精确时间开始的。我们发现，降低蛋白酶体的功能，APC，或Cdc20/Fizzy的纺锤体移动延迟。相反，在前中期灭活CDK会导致纺锤体提前移位。实验上将纺锤体移位与计时机制分离的结果是，有丝分裂纺锤体未完全组装的组件过早移位。我们的结论是，在这个系统中，有丝分裂纺锤体的不对称定位通常会延迟一小段时间，直到APC失活CDK，并且这种延迟确保纺锤体在完全组装之前不会开始移动。据我们所知，这是第一次证明在动物细胞的不对称分裂中，有丝分裂进程与纺锤体移位有关。我们推测，细胞周期和不对称细胞分裂之间的这种联系在进化上可能是保守的，因为在不同系统中的不对称细胞分裂过程中，有丝分裂纺锤体在类似的有丝分裂阶段发生移位。
The displacement of the mitotic spindle to one side of a cell is important for many cells to divide unequally. While recent progress has begun to unveil some of the molecular mechanisms of mitotic spindle displacement, far less is known about how spindle displacement is precisely timed. A conserved mitotic progression mechanism is known to time events in dividing cells, although this has never been linked to spindle displacement. This mechanism involves the anaphase-promoting complex (APC), its activator Cdc20/Fizzy, its degradation target cyclin, and cyclin-dependent kinase (CDK). Here we show that these components comprise a previously unrecognized timer for spindle displacement. In the Caenorhabditis elegans zygote, mitotic spindle displacement begins at a precise time, soon after chromosomes congress to the metaphase plate. We found that reducing the function of the proteasome, the APC, or Cdc20/Fizzy delayed spindle displacement. Conversely, inactivating CDK in prometaphase caused the spindle to displace early. The consequence of experimentally unlinking spindle displacement from this timing mechanism was the premature displacement of incompletely assembled components of the mitotic spindle. We conclude that in this system, asymmetric positioning of the mitotic spindle is normally delayed for a short time until the APC inactivates CDK, and that this delay ensures that the spindle does not begin to move until it is fully assembled. To our knowledge, this is the first demonstration that mitotic progression times spindle displacement in the asymmetric division of an animal cell. We speculate that this link between the cell cycle and asymmetric cell division might be evolutionarily conserved, because the mitotic spindle is displaced at a similar stage of mitosis during asymmetric cell divisions in diverse systems.