Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length.
Modeling reveals cortical dynein-dependent fluctuations in bipolar spindle length.
复制标题
DOI：
10.1016/j.bpj.2021.05.030
复制
发表时间：
2021-06
影响因子：
3.4
通讯作者：
Dayna L. Mercadante;Amity L Manning;S. Olson
中科院分区：
文献类型：
--
作者：
Dayna L. Mercadante;Amity L Manning;S. Olson
有丝分裂纺锤体的正确形成和维持是忠实的细胞分裂所必需的。虽然已经做了很多工作来了解有丝分裂纺锤体的关键分子组成部分的作用，确定力扰动的纺锤体的后果仍然是一个挑战。我们开发了一个计算框架占有丝分裂进程的最小力的要求。为了反映早期纺锤体的形成，我们对微管动力学和与主要力产生马达的相互作用进行了建模，排除了在有丝分裂后期占主导地位的染色体相互作用。我们直接整合我们的实验数据来定义和验证模型。然后，我们使用模拟来分析各个力分量随时间的变化以及它们与主轴动力学的关系，使其与以前发表的模型不同。我们表明，通过模型预测和生物操纵，而不是实现和保持一个恒定的双极纺锤体长度，在极到极的距离发生波动，与微管结合和力产生皮层动力蛋白相一致。我们的模型进一步预测，高动力蛋白活性所需的纺锤体双极性时，驱动蛋白-14（HSET）的活动也很高。据我们所知，我们的研究结果提供了新的洞察皮层动力蛋白在纺锤体双极调节的作用。
Proper formation and maintenance of the mitotic spindle is required for faithful cell division. Although much work has been done to understand the roles of the key molecular components of the mitotic spindle, identifying the consequences of force perturbations in the spindle remains a challenge. We develop a computational framework accounting for the minimal force requirements of mitotic progression. To reflect early spindle formation, we model microtubule dynamics and interactions with major force-generating motors, excluding chromosome interactions that dominate later in mitosis. We directly integrate our experimental data to define and validate the model. We then use simulations to analyze individual force components over time and their relationship to spindle dynamics, making it distinct from previously published models. We show through both model predictions and biological manipulation that rather than achieving and maintaining a constant bipolar spindle length, fluctuations in pole-to-pole distance occur that coincide with microtubule binding and force generation by cortical dynein. Our model further predicts that high dynein activity is required for spindle bipolarity when kinesin-14 (HSET) activity is also high. To the best of our knowledge, our results provide novel insight into the role of cortical dynein in the regulation of spindle bipolarity.