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Actin cable distribution and dynamics arising from cross-linking motor pulling and filament turnover

机译:肌动蛋白电缆的分布以及由交联电机牵引和灯丝周转引起的动力学

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摘要

The growth of fission yeast relies on the polymerization of actin filaments nucleated by formin For3p, which localizes at tip cortical sites. These actin filaments bundle to form actin cables that span the cell and guide the movement of vesicles toward the cell tips. A big challenge is to develop a quantitative understanding of these cellular actin structures. We used computer simulations to study the spatial and dynamical properties of actin cables. We simulated individual actin filaments as semiflexible polymers in three dimensions composed of beads connected with springs. Polymerization out of For3p cortical sites, bundling by cross-linkers, pulling by type V myosin, and severing by cofilin are simulated as growth, cross-linking, pulling, and turnover of the semiflexible polymers. With the foregoing mechanisms, the model generates actin cable structures and dynamics similar to those observed in live-cell experiments. Our simulations reproduce the particular actin cable structures in myoVΔ cells and predict the effect of increased myosin V pulling. Increasing cross-linking parameters generates thicker actin cables. It also leads to antiparallel and parallel phases with straight or curved cables, consistent with observations of cells overexpressing α-actinin. Finally, the model predicts that clustering of formins at cell tips promotes actin cable formation.
机译:裂变酵母的生长依赖于formin For3p成核的肌动蛋白丝的聚合,该蛋白位于皮层尖端。这些肌动蛋白丝捆绑在一起,形成跨细胞的肌动蛋白电缆,并引导囊泡向细胞尖端移动。一个巨大的挑战是发展对这些细胞肌动蛋白结构的定量理解。我们使用计算机模拟来研究肌动蛋白电缆的空间和动力学特性。我们将单个肌动蛋白丝模拟为三个柔韧性聚合物,由三个与弹簧连接的小珠组成。从For3p皮质位点聚合出来,通过交联剂进行束缚,通过V型肌球蛋白拉动和通过纤丝蛋白切断均被模拟为半柔性聚合物的生长,交联,拉动和周转。利用上述机制,该模型生成的肌动蛋白电缆结构和动力学与在活细胞实验中观察到的相似。我们的模拟再现了myoVΔ细胞中特定的肌动蛋白电缆结构,并预测了增加的肌球蛋白V拉动效应。交联参数的增加会生成较粗的肌动蛋白电缆。它也导致直线或弯曲电缆出现反平行和平行相,这与观察到过表达α-肌动蛋白的细胞一致。最后,该模型预测在细胞尖端的福尔马林聚集会促进肌动蛋白电缆的形成。

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