Centrosome age breaks spindle size symmetry even in cells thought to divide symmetrically.

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-08-05 Epub Date: 2024-07-16 DOI:10.1083/jcb.202311153
Alexandre Thomas, Patrick Meraldi
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Abstract

Centrosomes are the main microtubule-organizing centers in animal cells. Due to the semiconservative nature of centrosome duplication, the two centrosomes differ in age. In asymmetric stem cell divisions, centrosome age can induce an asymmetry in half-spindle lengths. However, whether centrosome age affects the symmetry of the two half-spindles in tissue culture cells thought to divide symmetrically is unknown. Here, we show that in human epithelial and fibroblastic cell lines centrosome age imposes a mild spindle asymmetry that leads to asymmetric cell daughter sizes. At the mechanistic level, we show that this asymmetry depends on a cenexin-bound pool of the mitotic kinase Plk1, which favors the preferential accumulation on old centrosomes of the microtubule nucleation-organizing proteins pericentrin, γ-tubulin, and Cdk5Rap2, and microtubule regulators TPX2 and ch-TOG. Consistently, we find that old centrosomes have a higher microtubule nucleation capacity. We postulate that centrosome age breaks spindle size symmetry via microtubule nucleation even in cells thought to divide symmetrically.

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即使在被认为是对称分裂的细胞中,中心体的年龄也会打破纺锤体大小的对称性。
中心体是动物细胞中主要的微管组织中心。由于中心体复制的半保守性,两个中心体的年龄不同。在非对称干细胞分裂中,中心体年龄可导致半纺锤体长度的非对称性。然而,在被认为是对称分裂的组织培养细胞中,中心体年龄是否会影响两个半纺锤体的对称性尚不清楚。在这里,我们发现在人类上皮细胞和成纤维细胞系中,中心体年龄会造成轻微的纺锤体不对称,从而导致细胞子粒大小不对称。在机理层面,我们发现这种不对称依赖于与有丝分裂激酶 Plk1 结合的 cenexin 池,它有利于微管成核组织蛋白 pericentrin、γ-tubulin 和 Cdk5Rap2 以及微管调节剂 TPX2 和 ch-TOG 在老的中心体上优先积累。同样,我们发现老的中心体具有更高的微管成核能力。我们推测,即使在被认为是对称分裂的细胞中,中心体的年龄也会通过微管成核打破纺锤体大小的对称性。
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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
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