A surprising Twist to cell dissemination

M oyle et al. de-s c r i b e h ow the C. elegans BUB-1 kinase helps recruit the spindle checkpoint proteins MAD-1 and MAD-2 to unattached kinetochores. During mitosis, the MAD-1–MAD-2 complex binds to kinetochores that haven't attached to the spindle and generates a signal that prevents cells from entering anaphase until the correct attachments are formed. Several kinetochore proteins are required to localize MAD-1– MAD-2 to unattached kinetochores in vivo, but whether any of these proteins recruit the checkpoint complex directly is unknown. Moyle et al. screened a library of kinetochore proteins and found that C. elegans MAD-1 interacted with BUB-1, a kinase required for MAD-1–MAD-2 localization. Mutations in MAD-1's central coiled-coil domain disrupted the protein's interaction with BUB-1 and inhibited the recruitment of MAD-1 and MAD-2 to unattached kinetochores in worms, thereby preventing them from activating the spindle checkpoint and delaying anaphase. MAD-1 interacted with BUB-1's C-terminal kinase domain, and mutations in this domain blocked MAD-1's recruitment to unattached kinetochores. But BUB-1's kinase activity wasn't required for MAD-1's localization, suggesting that BUB-1 recruits MAD-1 to kinetochores directly. Senior author Arshad Desai now wants to investigate how other kinetochore proteins, such as the microtubule-binding protein Ndc80, contribute to MAD-1–MAD-2 recruitment and ensure that the complex is removed once kinetochores are correctly attached to the mitotic spindle. H arada et al. describe how nuclear lamins affect the ability of migrating cells to squeeze through tissues and survive the resulting stress. Migrating cells must maneuver their large and chromatin-packed nuclei through tiny gaps in the surrounding tissue. A-and B-type lamins assemble in the nuclear periphery and help determine the organelle's mechanical properties, but whether these proteins affect cell migration is unclear. Harada et al. tested the role of lamin-A in several different cell types. Partially reducing lamin-A levels enhanced the ability of cells to move through extracellular matrix containing small, 3-μm pores, whereas overexpressing the protein inhibited cell migration. Cells that expressed stoichiometrically high amounts of lamin-B were particularly sensitive to changes in lamin-A levels. The researchers found that nuclei containing low amounts of lamin-A were softer, allowing them to squeeze through tiny pores and—due to the spring-like properties of lamin-B—return to their normal shape on the other side. In contrast, high lamin-A levels made nuclei stiff and harder to maneuver, a property that could help keep mesenchymal stem cells, which express large amounts of lamin-A, anchored in their …