Cortical dynein drives centrosome clustering in cells with centrosome amplification.
Cortical dynein drives centrosome clustering in cells with centrosome amplification.
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DOI：
10.1091/mbc.e22-07-0296
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发表时间：
2023-05-15
影响因子：
3.3
通讯作者：
Manning, Amity L.
中科院分区：
文献类型：
--
作者：
Mercadante, Dayna L.;Aaron, William A.;Olson, Sarah D.;Manning, Amity L.
在细胞分裂过程中，微管成核和组织细胞器，称为中心体，是有丝分裂纺锤体的关键组成部分。在具有两个中心体的细胞中，每个中心体作为微管的锚点，导致双极纺锤体的形成和通过双极细胞分裂的进展。当存在额外的中心体时，多极纺锤体形成，并且父细胞可以分裂成两个以上的子细胞。从多极分裂产生的细胞是不能存活的，因此额外中心体的聚集和向双极分裂的进展是具有额外中心体的细胞中存活力的关键决定因素。我们结合联合收割机的实验方法与计算建模，以确定皮质动力蛋白在中心体聚类中的作用。我们表明，当皮质动力蛋白分布或活动受到实验干扰时，中心体聚集失败，多极纺锤体占主导地位。我们的模拟进一步揭示了中心体聚集对皮层上动力蛋白的分布是敏感的。总之，这些结果表明，单独的动力蛋白的皮质定位是不够的有效的中心体聚类，而是动态重新定位的动力蛋白从细胞的一侧到另一侧，在整个有丝分裂促进及时的聚类和双极细胞分裂的细胞与额外的中心体。
During cell division, the microtubule nucleating and organizing organelle, known as the centrosome, is a critical component of the mitotic spindle. In cells with two centrosomes, each centrosome functions as an anchor point for microtubules, leading to the formation of a bipolar spindle and progression through a bipolar cell division. When extra centrosomes are present, multipolar spindles form and the parent cell may divide into more than two daughter cells. Cells that are born from multipolar divisions are not viable, and hence clustering of extra centrosomes and progression to a bipolar division are critical determinants of viability in cells with extra centrosomes. We combine experimental approaches with computational modeling to define a role for cortical dynein in centrosome clustering. We show that centrosome clustering fails and multipolar spindles dominate when cortical dynein distribution or activity is experimentally perturbed. Our simulations further reveal that centrosome clustering is sensitive to the distribution of dynein on the cortex. Together, these results indicate that dynein’s cortical localization alone is insufficient for effective centrosome clustering and, instead, dynamic relocalization of dynein from one side of the cell to the other throughout mitosis promotes timely clustering and bipolar cell division in cells with extra centrosomes.