A Gradient in Metaphase Tension Leads to a Scaled Cellular Response in Mitosis
A Gradient in Metaphase Tension Leads to a Scaled Cellular Response in Mitosis
复制标题
DOI：
10.1016/j.devcel.2019.01.018
复制
发表时间：
2019-04-08
影响因子：
11.8
通讯作者：
Gardner, Melissa K.
中科院分区：
文献类型：
--
作者：
Mukherjee, Soumya;Sandri, Brian J.;Gardner, Melissa K.
在有丝分裂过程中，马达蛋白与微管结合，施加推力，建立有丝分裂纺锤体。这些推力在连接相对附着的姐妹染色单体的染色质中产生相反的张力，其然后可以作为机械信号以确保有丝分裂期间染色体分离的保真度。然而，张力在有丝分裂细胞信号传导中的作用仍然存在争议。在这项研究中，我们产生了一个梯度的张力超过多个同基因芽殖酵母细胞系，通过遗传改变电机为基础的主轴力的大小。我们发现，在张力梯度下降导致的动粒脱离和后期染色体的错误分离，并在中期时间的比率梯度增加。模拟和实验表明，这些张力反应起源于张力依赖的动粒磷酸化梯度。我们的结论是，细胞是精致的调整到张力的大小作为一个信号，以检测潜在的染色体分离错误在有丝分裂。
During mitosis, motor proteins associate with microtubules to exert pushing forces that establish a mitotic spindle. These pushing forces generate opposing tension in the chromatin that connects oppositely attached sister chromatids, which may then act as a mechanical signal to ensure the fidelity of chromosome segregation during mitosis. However, the role of tension in mitotic cellular signaling remains controversial. In this study, we generated a gradient in tension over multiple isogenic budding yeast cell lines by genetically altering the magnitude of motor-based spindle forces. We found that a decreasing gradient in tension led to an increasing gradient in the rates of kinetochore detachment and anaphase chromosome mis-segregration, and in metaphase time. Simulations and experiments indicated that these tension responses originate from a tension-dependent kinetochore phosphorylation gradient. We conclude that the cell is exquisitely tuned to the magnitude of tension as a signal to detect potential chromosome segregation errors during mitosis.