Centrosome age breaks spindle size symmetry even in “symmetrically” dividing cells

Abstract

AbstractCentrosomes are the main microtubule organizing center in animal cells. Due to the semi-conservative 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 subtle spindle asymmetry that leads to asymmetric cell daughter sizes. At the mechanistic level, we show that this asymmetry depends on the preferential accumulation on old centrosomes of the microtubule nucleation-organizing proteins pericentrin, γ-tubulin, Cdk5Rap2, and TPX2, under the control of a cenexin-bound pool of the mitotic kinase Plk1. Moreover, we find that old centrosomes have a higher microtubule nucleation capacity. We therefore postulate that centrosome age breaks spindle size symmetry via microtubule nucleation even in cells thought to divide symmetrically.