Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast.
Physical determinants of bipolar mitotic spindle assembly and stability in fission yeast.
复制标题
双极有丝分裂纺锤体组件的物理决定因素和裂变酵母中的稳定性。
DOI：
10.1126/sciadv.1601603
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发表时间：
2017-01
期刊：
影响因子：
13.6
通讯作者：
Betterton MD
中科院分区：
文献类型：
--
作者：
Blackwell R;Edelmaier C;Sweezy-Schindler O;Lamson A;Gergely ZR;O'Toole E;Crapo A;Hough LE;McIntosh JR;Glaser MA;Betterton MD
一个物理模型，展示从头双极纺锤体组装是用来研究纺锤体双极性的机制。有丝分裂纺锤体使用优雅的双极结构以高保真度分离重复的染色体。双极主轴从单极初始条件形成;这是主轴必须解决的最基本的构造问题。微管、马达和交联剂对双极性很重要，但纺锤体组装所必需和充分的机制仍然未知。我们描述了一个物理模型，表现出从头双极纺锤体的形成。我们从分裂酵母纺锤体极体大小和微管数量、驱动蛋白-5马达、驱动蛋白-14马达和被动交联剂的物理性质开始。我们的模型结果与我们在裂变酵母中的实验定量一致，从而建立了一个最小的系统来询问集体自组装。通过改变我们的模型的功能，我们确定了一组功能的产生和稳定的纺锤体双极性。当驱动蛋白-5马达存在时，它们的双向性是必不可少的，但是纺锤体可以在单独的被动交联剂存在下形成。我们还确定了纺锤体组装的特征失败的状态-持久的，X纺锤体，分离的紫苑，和短纺锤体，这是避免创建和维护的反平行微管重叠。我们的模型可以指导识别新的，多方面的策略，以诱导有丝分裂灾难，这些将构成癌症化疗的新策略。
A physical model that exhibits de novo bipolar spindle assembly is used to study the mechanisms of spindle bipolarity. Mitotic spindles use an elegant bipolar architecture to segregate duplicated chromosomes with high fidelity. Bipolar spindles form from a monopolar initial condition; this is the most fundamental construction problem that the spindle must solve. Microtubules, motors, and cross-linkers are important for bipolarity, but the mechanisms necessary and sufficient for spindle assembly remain unknown. We describe a physical model that exhibits de novo bipolar spindle formation. We began with physical properties of fission-yeast spindle pole body size and microtubule number, kinesin-5 motors, kinesin-14 motors, and passive cross-linkers. Our model results agree quantitatively with our experiments in fission yeast, thereby establishing a minimal system with which to interrogate collective self-assembly. By varying the features of our model, we identify a set of functions essential for the generation and stability of spindle bipolarity. When kinesin-5 motors are present, their bidirectionality is essential, but spindles can form in the presence of passive cross-linkers alone. We also identify characteristic failed states of spindle assembly—the persistent monopole, X spindle, separated asters, and short spindle, which are avoided by the creation and maintenance of antiparallel microtubule overlaps. Our model can guide the identification of new, multifaceted strategies to induce mitotic catastrophes; these would constitute novel strategies for cancer chemotherapy.