Modeling Contractile Ring Constriction in Fission Yeast

 描述（由申请方提供）：胞质分裂是细胞周期的最后阶段，此时细胞质被切割成两部分。正确的时间和位置的分裂是细胞分裂，导致两个正常的子细胞的必要条件。在动物、真菌和变形虫细胞中，胞质分裂涉及肌动球蛋白收缩环的收缩。裂殖酵母裂殖酵母的收缩环特别适合于定量建模，因为环蛋白特别好地表征。然而，产生环张力和收缩环的机制还没有很好地理解。从第一阶段的支持，我们已经开发了一个工作的计算机模拟框架的裂变酵母收缩环，第一个工作方法来测量环张力实验，和一个模型的分隔过程，伴随着环收缩。该研究的第一个目的是建立一个完全动态的3D模拟，以捕捉环的超微结构。我们将实现裂变酵母环中的两种肌球蛋白-II亚型Myo 2和Myp 2的详细组织，以及肌动蛋白、肌动蛋白成核剂β、肌动蛋白交联剂和其他关键组分。模拟将通过计算环张力和组件运动来测试假设的组织，以便与实验值进行直接比较。每个组织将被测试结构不稳定性，特别是在环蛋白突变的环模拟。的 模型还将模拟在酵母原生质体、细胞和细胞中滑动的环中的详细组件运动。 其壁已被去除，用于与实验成像的滑环进行比较。第二个目标是建立一个完整的裂殖酵母环收缩和分离模型。在耦合的模拟方案中，隔膜形状决定了环的演变表面，它是连接，而时空变化的环张力反馈到隔膜的增长。将整合模型的张力、组织稳定性、隔膜形态和其他输出与实验进行比较。第三个目的是模拟分离的分裂酵母细胞动力学环的行为，如在实验中使用透性化的酵母原生质体所研究的。在这些情况下，正常的组分周转被阻断，因为新的组分不结合环，并且环通常从质膜上部分脱离。因此，环在这些条件下的行为探讨了翻转和锚定在环的张力产生和收缩机制中的作用。环模拟将在没有组件绑定的情况下运行，并使用部分锚定的环，并将行为与实验进行比较。

 DESCRIPTION (provided by applicant): Cytokinesis is the final stage of the cell cycle when the cytoplasm is cleaved into two parts. Proper timing and location of the cleavage is essential for cell division to result in two normal daughter cells. In animal, fungal and amoeboid cells cytokinesis involves constriction of an actomyosin contractile ring. The contractile ring of fissio yeast Schizosaccharomyces pombe is particularly amenable to quantitative modeling, as the ring proteins are particularly well characterized. However the mechanisms that generate ring tension and constrict the ring are not well understood. From the first period of support, we have developed a working computer simulation framework for the fission yeast contractile ring, the first working method to measure ring tension experimentally, and a model of the septation process that accompanies ring constriction. The first Aim of the proposed research is to build a fully dynamic 3D simulation to capture the ultrastructure of the ring. We will implement detailed organizations of the two myosin-II isoforms in the fission yeast ring, Myo2 and Myp2, together with actin, the actin nucleator formin, actin crosslinkers and other key components. The simulations will test hypothesized organizations by calculating ring tension and component motions for direct comparison with experimental values. Each organization will be tested for structural instabilities, particularly in simulations of rings with mutations in ring proteins. The model will also simulate detailed component motions in rings that slide in yeast protoplasts, cells whose walls have been removed, for comparison with experimentally imaged sliding rings. The second Aim is to develop an integrated model of fission yeast ring constriction and septation. In the coupled simulation scheme the septum shape dictates to the ring the evolving surface to which it is attached, while spatiotemporally varying ring tension feeds back to septum growth. Tensions, organizational stability, septum morphology and other outputs of the integrated model will be compared to experiment. The third Aim is to model the behavior of isolated fission yeast cytokinetic rings, as studied in experiments using permeabilized yeast protoplasts. In these circumstances normal component turnover is blocked, as new components do not bind the ring, and rings often become partially unanchored from the plasma membrane. As a result, the behavior of rings in these conditions probes the role of turnover and anchoring in the mechanisms of tension production and constriction of the ring. The ring simulations will be run without component binding, and with partially anchored rings, and the behavior compared to experiments.