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J Cell Biol. 2010 March 22; 188(6): 752.
PMCID: PMC2845067
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A team of rivals at the kinetochore

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PPI is lost from kinetochores when its binding site on KNL1 is mutated (right).

Protein phosphatase I (PPI) is specifically recruited to kinetochores to counteract the Aurora B kinase, report Liu et al. The opposing enzymes combine to ensure chromosomes segregate correctly in mitosis.

In metaphase, the kinetochores of sister chromatids must connect to microtubules emanating from opposite spindle poles. Incorrect attachments are eliminated by Aurora B, which phosphorylates kinetochore proteins to reduce their microtubule-binding capacity. Correct attachments generate tension and pull the kinetochore proteins out of Aurora B's reach, but phosphate groups added by the kinase must be removed to stabilize the kinetochore–microtubule interaction. PPI is a good candidate for this job, but its role at kinetochores has been difficult to study as it has multiple functions in the cell.

Liu et al. found that the kinetochore protein KNL1 binds and recruits PPI. Preventing PPI targeting to kinetochores by mutating KNL1 resulted in increased phosphorylation of Aurora B substrates and unstable microtubule attachments, even at kinetochores aligned correctly on the mitotic spindle. PPI is therefore needed to reverse Aurora B activity and stabilize microtubules at kinetochores, but PPI's recruitment is itself regulated by Aurora B, the researchers found. Phosphorylation of KNL1 blocked its association with PP1, indicating that Aurora B excludes PP1 from kinetochores until correct attachments and tension pull KNL1 away from the kinase.

Small amounts of PPI could then dephosphorylate KNL1 and promote the recruitment of further PPI molecules, says author Michael Lampson. This might make the transition between stable and unstable microtubule binding sharper, a proposition Lampson and co-author Iain Cheeseman now want to investigate using phospho-site mutants of KNL1.

References


Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press