Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.
J Cell Sci. 2023 Mar 1;136(5). doi: 10.1242/jcs.259969. Epub 2022 Oct 6.
In common with other actomyosin contractile cellular machineries, actin turnover is required for normal function of the cytokinetic contractile ring. Cofilin is an actin-binding protein contributing to turnover by severing actin filaments, required for cytokinesis by many organisms. In fission yeast cofilin mutants, contractile rings suffer bridging instabilities in which segments of the ring peel away from the plasma membrane, forming straight bridges whose ends remain attached to the membrane. The origin of bridging instability is unclear. Here, we used molecularly explicit simulations of contractile rings to examine the role of cofilin. Simulations reproduced the experimentally observed cycles of bridging and reassembly during constriction, and the occurrence of bridging in ring segments with low density of the myosin II protein Myo2. The lack of cofilin severing produced ∼2-fold longer filaments and, consequently, ∼2-fold higher ring tensions. Simulations identified bridging as originating in the boosted ring tension, which increased centripetal forces that detached actin from Myo2, which was anchoring actin to the membrane. Thus, cofilin serves a critical role in cytokinesis by providing protection from bridging, the principal structural threat to contractile rings.
与其他肌球蛋白收缩细胞机械装置一样，肌动蛋白周转率对于胞质分裂收缩环的正常功能是必需的。丝切蛋白是一种肌动蛋白结合蛋白，通过切断肌动蛋白丝促进周转率，许多生物的胞质分裂都需要丝切蛋白。在有丝分裂酵母丝切蛋白突变体中，收缩环会出现桥接不稳定性，环的片段会从质膜上剥离，形成笔直的桥，其末端仍附着在膜上。桥接不稳定性的起源尚不清楚。在这里，我们使用收缩环的分子显式模拟来研究丝切蛋白的作用。模拟再现了实验观察到的收缩过程中桥接和重组装的循环，以及在肌球蛋白 II 蛋白 Myo2 密度较低的环段中发生桥接的情况。丝切蛋白的缺失导致肌动蛋白丝延长约 2 倍，因此环张力增加约 2 倍。模拟表明，桥接起源于增强的环张力，这种张力增加了向心力，使肌动蛋白从锚定肌动蛋白到质膜的 Myo2 上脱离。因此，丝切蛋白通过提供对桥接的保护，在胞质分裂中起着至关重要的作用，桥接是对收缩环的主要结构威胁。
