Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells.
Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells.
复制标题
皮质动力蛋白的聚集调节人类有丝分裂细胞中纺锤体方向的机制。
DOI：
10.1101/2023.09.11.557210
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Needleman,DanielJ
中科院分区：
文献类型：
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作者：
Anjur-Dietrich,MayaI;Hererra,VicenteGomez;Farhadifar,Reza;Wu,Haiyin;Merta,Holly;Bahmanyar,Shirin;Shelley,MichaelJ;Needleman,DanielJ
由于在哺乳动物系统中缺乏直接的机械测量，对人类细胞中纺锤体的定向力仍然知之甚少。我们使用磁镊来测量人类有丝分裂纺锤体上的力。结合纺锤体的测量旋转阻力，激光消融星形微管后的旋转速度，以及消融微管数量的估计，揭示了每个接触细胞皮质的微管受到约1 pN的拉力，这表明每个微管都是由单个动力蛋白马达拉动的。我们发现，在细胞皮质的动力蛋白的浓度和程度的动力蛋白集群的纺锤体的旋转阻力的关键决定因素，从细胞质粘度，我们解释使用生物病理学为基础的数学模型的贡献很小。这项工作揭示了星形微管上的拉力如何决定纺锤体方向的力学，并证明了皮质动力蛋白聚集的核心作用。
The forces which orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle’s measured resistance to rotation, the speed it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ~1 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle’s resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.