Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Translational Research Centre in Onco-hematology, Faculty of Medicine, University of Geneva , Geneva, Switzerland.
J Cell Biol. 2024 Aug 5;223(8). doi: 10.1083/jcb.202311153. Epub 2024 Jul 16.
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质，两个中心体的年龄不同。在不对称的干细胞分裂中，中心体的年龄可以诱导半纺锤体长度的不对称。然而，在组织培养细胞中，人们认为这些细胞是对称分裂的，中心体的年龄是否会影响两个半纺锤体的对称性尚不清楚。在这里，我们表明在人类上皮细胞和成纤维细胞系中，中心体的年龄会产生轻微的纺锤体不对称性，从而导致细胞子代大小的不对称。在机制水平上，我们表明这种不对称性依赖于 cenexin 结合的有丝分裂激酶 Plk1 池，它有利于微管核蛋白中心体蛋白、γ-微管蛋白和 Cdk5Rap2 以及微管调节剂 TPX2 和 ch-TOG 在旧中心体上的优先积累。一致地，我们发现旧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，中心体的年龄也可以通过微管成核打破纺锤体大小的对称性。
