A paradigm for coordinating chromosome movement on the mitotic spindle

Movements of chromosomes during mitosis are achieved by their attachment to the bipolar mitotic spindle, whose assembly is initiated from a pair of spindle poles. Chromosomes attach to the microtubule spindle at proteinaceous structures known as kinetochores. A long-standing question in the field is: how is chromosome movement on the mitotic spindle coordinated?

 

During my postdoctoral work we demonstrated that chromosome motion and stable microtubule capture is controlled by the sequential action of Aurora kinase and Protein phosphatase-1 (PP1) on the kinetochore motor protein Centromere Protein-E (CENP-E). CENP-E is phosphorylated at a single site at the spindle poles by Aurora kinases and phosphorylation is required to promote chromosome congression. PP1 binds to CENP-E via a motif overlapping this phosphorylation site, and binding is disrupted by Aurora phosphorylation. Thus, following chromosome alignment CENP-E is dephosphorylated and bound by Protein phosphatase-1 (PP1). Localized PP1 delivery by CENP-E to the outer kinetochore was shown to be required for stable microtubule capture by chromosomes congressed from the poles (Kim, Holland et al., Cell, 2010). This work provides a paradigm to explain how localized gradients of kinase and phosphatase activity provide positional information that coordinate chromosome movement and microtubule attachment.