Cell Size Determines the Strength of the Spindle Assembly Checkpoint during Embryonic Development.
Cell Size Determines the Strength of the Spindle Assembly Checkpoint during Embryonic Development.
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DOI：
10.1016/j.devcel.2016.01.003
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发表时间：
2016-02-08
影响因子：
11.8
通讯作者：
Morgan DO
中科院分区：
文献类型：
--
作者：
Galli M;Morgan DO
当染色体未正确附着到有丝分裂纺锤体的微管时，纺锤体组装检查点（SAC）会延迟有丝分裂进程。细胞在 SAC 激活后延迟有丝分裂进展的程度差异很大。为了探索决定不同细胞中检查点强度的机制，我们系统地测量了秀丽隐杆线虫胚胎发生不同阶段微管破坏引起的有丝分裂延迟。引人注目的是，我们观察到每轮划分后 SAC 强度逐渐增加。对改变细胞大小或倍性的突变体的分析表明，SAC 强度主要由细胞大小和着丝粒数量决定。这些发现在体内提供了明确的证据，表明着丝粒与细胞质的比率决定了 SAC 的强度，为为什么细胞的 SAC 反应表现出如此大的变化提供了新的见解。
The spindle assembly checkpoint (SAC) delays mitotic progression when chromosomes are not properly attached to microtubules of the mitotic spindle. Cells vary widely in the extent to which they delay mitotic progression upon SAC activation. To explore the mechanisms that determine checkpoint strength in different cells, we systematically measured the mitotic delay induced by microtubule disruption at different stages of embryogenesis in Caenorhabditis elegans. Strikingly, we observed a gradual increase in SAC strength after each round of division. Analysis of mutants that alter cell size or ploidy revealed that SAC strength is determined primarily by cell size and the number of kinetochores. These findings provide clear evidence in vivo that the kinetochore-to-cytoplasm ratio determines the strength of the SAC, providing new insights into why cells exhibit such large variations in their SAC responses.