Arf and Miz1 cause cells to lose their grip

A team of rivals at the kinetochore P rotein 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 ki-nase must be removed to stabilize the kinetochore–microtubule interaction. PPI is a good candidate for this job, but its role at kinetochores has been diffi cult 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. Disuse TWEAKs muscle loss M ittal et al. identify a cytokine signaling pathway that induces the breakdown of disused skeletal muscle. Blocking this pathway could prevent immobilized patients from losing their muscle tissue. Skeletal muscle wastes away when its activity is reduced by—for example—the loss of stimulatory motor neurons. Although the mechanism by which muscle fi bers break down is understood fairly well, how the process is triggered remains unknown. The TNF-related cytokine TWEAK can induce muscle loss, but whether it does so in disused muscle is unclear. Mittal et al. compared how mice expressing different amounts of TWEAK responded when the nerve innervating their hind legs was severed. Mice producing excess TWEAK lost their muscle more quickly than wild-type animals, whereas mice lacking this cytokine were largely protected from muscle …