Managing tension

ells only exit metaphase if all their chromosomes are both attached and under tension from microtubules of the bipolar spindle, which pull on sister kinetochores that face in opposite directions. report that tension creation requires Mtw1p and associated proteins, and is sensed by the conserved Ipl1p/Aurora B protein kinase. In the current model for Ipl1p action, many chromosomes initially have both kinetochores attached to a single pole. The resulting lack of tension turns on Ipl1p, which detaches kinetochores so that they are free to have another go at attaching to opposite poles. This detaching activity can be mimicked by adding low doses of microtubule-depolymerizing drugs to cells lacking Ipl1p. But what feeds in to Ipl1p? Most kine-tochore problems cause attachment-related defects and delays, but cells that don't generate tension should rely specifically on Ipl1p to delay the cell cycle. The Seattle group found that Mtw1p and several associated proteins fit the bill. In cells lacking Mtw1p, chromosomes floated free, presumably after Ipl1p detected the apparent lack of tension and set them loose. Sure enough, removing Ipl1p from the mutant cells allowed these chromosomes to maintain their attachments. Just how Mtw1p creates tension is unknown. It could convert initial side-on microtubule attachments at the kineto-chore into force-producing end-on attachments, or stimulate microtubule dynamics that pull on kinetochores. It will be easier to differentiate between these and other models after determining the compositional and structural differences between attached and unattached kinetochores. Once attachment is complete, the connection between sister chromatids is dissolved by separase, leading to ana-phase movement and an immediate loss in tension. It would be disastrous if Ipl1p now took over, sensed the lack of tension , and caused a mass dumping of chromosomes before they are pulled to opposite ends of the cell. Ipl1p does indeed leave, in a complex with the inner centromere protein (INCENP) Sli15p. It remains unclear what triggers the departure from kinetochores. But Gislene Pereira and Elmar Schiebel (University of Manchester, Manchester, UK) now shed some light on what eventually targets Ipl1p–Sli15p to spindles. They find that separase activates some Cdc14p phosphatase so that it can dephosphory-late Sli15p, thus directing the complex to the spindle where it can recruit proteins that stabilize the elongating spindle. ᭿ utoimmunity seems like a model for the immune system gone awry, but things could be a lot worse, say Gizi Wildbaum, They find that the immune system responds to …