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.

中文翻译：

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即使在被认为对称分裂的细胞中，中心体年龄也会破坏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。在不对称干细胞分裂中，中心体年龄会引起半纺锤体长度的不对称。然而，中心体年龄是否影响被认为对称分裂的组织培养细胞中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，从而导致细胞子代大小不对称。在机制水平上，我们表明这种不对称性取决于有丝分裂激酶 Plk1 的 cenexin 结合库，有利于微管成核组织蛋白 Pericentrin、γ-tubulin 和 Cdk5Rap2 以及微管调节因子在旧中心体上优先积累TPX2 和 ch-TOG。一致地，我们发现旧中心体具有更高的微管成核能力。我们假设中心体年龄通过微管成核打破纺锤体尺寸对称性，即使在被认为对称分裂的细胞中也是如此。