Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Dev Cell. 2019 Apr 8;49(1):63-76.e10. doi: 10.1016/j.devcel.2019.01.018. Epub 2019 Feb 21.
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.
在有丝分裂过程中，动力蛋白与微管结合，产生推动力，从而建立纺锤体。这些推力在连接对向附着的姐妹染色单体的染色质中产生相反的张力，这可能作为一种机械信号，以确保有丝分裂过程中染色体分离的保真度。然而，张力在有丝分裂细胞信号转导中的作用仍然存在争议。在这项研究中，我们通过遗传改变基于马达的纺锤体力的大小，在多个同基因出芽酵母细胞系中产生了张力的梯度。我们发现，张力的递减梯度导致动粒脱离率和后期染色体错误分离率以及中期时间的增加梯度。模拟和实验表明，这些张力反应源于张力依赖性动粒磷酸化梯度。我们的结论是，细胞对张力的大小非常敏感，作为检测有丝分裂过程中潜在染色体分离错误的信号。
