Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression

Chromosome congression is crucial for accurate cell division, with key roles played by kinetochore components such as CENP-E/kinesin-7 and Aurora B kinase. However, Aurora kinases can both inhibit and promote congression, suggesting the presence of a larger, yet poorly understood, signaling network. Our study demonstrates that centrosomes primarily inhibit congression initiation when CENP-E is inactive or absent by regulating the activity of kinetochore components. Depleting centrioles via Plk4 inhibition allows chromosomes near acentriolar poles to initiate congression independently of CENP-E. In contrast, at centriolar poles high Aurora A activity enhances Aurora B activity, increasing phosphorylation of microtubule-binding proteins at kinetochores and preventing stable microtubule attachments in the absence of CENP-E. Conversely, inhibiting Aurora A reduces Aurora B activity, enabling congression initiation even without CENP-E. These findings suggest a feedback network involving Aurora kinases and CENP-E that regulates timing of chromosome movement by modulating kinetochore-microtubule interactions, with centrosomes and the Aurora A activity gradient providing critical spatial cues for the network’s function.