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

Abstract

Chromosome congression is crucial for accurate cell division, with key roles played by kinetochore components, the molecular motor CENP-E/kinesin-7, and Aurora B kinase. However, Aurora B kinase can both inhibit and promote congression, suggesting the presence of a larger signaling network. Our study demonstrates that centrosomes inhibit congression initiation when CENP-E is inactive by regulating the activity of kinetochore components. Depletion of centrioles via Plk4 kinase inhibition allows chromosomes near acentriolar poles to initiate congression independently of CENP-E. At centriolar poles, high Aurora A kinase enhances Aurora B activity, increasing phosphorylation of microtubule-binding proteins at kinetochores and preventing stable microtubule attachments in the absence of CENP-E. Conversely, inhibition of Aurora A or expression of a dephosphorylatable mutant of the kinetochore microtubule-binding protein Hec1 enables congression initiation without CENP-E. We propose a negative feedback mechanism involving Aurora kinases and CENP-E that regulates the timing of chromosome movement by modulating kinetochore-microtubule attachments and fibrous corona expansion, with the Aurora A activity gradient providing critical spatial cues for the network's function.