Dorn Jonas F, Zhang Li, Phi Tan-Trao, Lacroix Benjamin, Maddox Paul S, Liu Jian, Maddox Amy Shaub
Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, Canada.
Institut Jacques Monod, 75205 Paris cedex 13, France.
Mol Biol Cell. 2016 Apr 15;27(8):1286-99. doi: 10.1091/mbc.E15-06-0374. Epub 2016 Feb 24.
During cytokinesis, the cell undergoes a dramatic shape change as it divides into two daughter cells. Cell shape changes in cytokinesis are driven by a cortical ring rich in actin filaments and nonmuscle myosin II. The ring closes via actomyosin contraction coupled with actin depolymerization. Of interest, ring closure and hence the furrow ingression are nonconcentric (asymmetric) within the division plane across Metazoa. This nonconcentricity can occur and persist even without preexisting asymmetric cues, such as spindle placement or cellular adhesions. Cell-autonomous asymmetry is not explained by current models. We combined quantitative high-resolution live-cell microscopy with theoretical modeling to explore the mechanistic basis for asymmetric cytokinesis in theCaenorhabditis eleganszygote, with the goal of uncovering basic principles of ring closure. Our theoretical model suggests that feedback among membrane curvature, cytoskeletal alignment, and contractility is responsible for asymmetric cytokinetic furrowing. It also accurately predicts experimental perturbations of conserved ring proteins. The model further suggests that curvature-mediated filament alignment speeds up furrow closure while promoting energy efficiency. Collectively our work underscores the importance of membrane-cytoskeletal anchoring and suggests conserved molecular mechanisms for this activity.
在胞质分裂过程中，细胞在分裂为两个子细胞时会经历剧烈的形态变化。胞质分裂中的细胞形态变化由富含肌动蛋白丝和非肌肉肌球蛋白II的皮质环驱动。该环通过肌动球蛋白收缩以及肌动蛋白解聚而闭合。有趣的是，在整个后生动物的分裂平面内，环的闭合以及因此产生的沟的侵入是非同心的（不对称的）。即使没有预先存在的不对称线索，如纺锤体位置或细胞黏附，这种非同心性也可能发生并持续存在。当前模型无法解释细胞自主不对称现象。我们将定量高分辨率活细胞显微镜技术与理论建模相结合，以探索秀丽隐杆线虫受精卵中不对称胞质分裂的机制基础，目的是揭示环闭合的基本原理。我们的理论模型表明，膜曲率、细胞骨架排列和收缩性之间的反馈是不对称胞质分裂沟形成的原因。它还准确预测了保守环蛋白的实验扰动。该模型进一步表明，曲率介导的丝排列加快了沟的闭合，同时提高了能量效率。我们的工作共同强调了膜 - 细胞骨架锚定的重要性，并提出了这种活动的保守分子机制。
