Mad2 is all the rage in mitotic cells. The protein is a key part of the mitotic checkpoint, and now Lee et al. reveal that it also controls cytokinesis.
Mad2 detains cells in metaphase until the mitotic spindle connects to every chromosome. But cells often fail to divide if Mad2 goes awry. The reason for this, researchers have suggested, is that the chromosomes didn't separate properly. However, it's possible that Mad2 also helps manage cell division. Lee et al. had already discovered a possible link to cytokinesis—Mad2 latches onto MKlp2, a molecular motor. At the end of metaphase, MKlp2 lugs the chromosome passenger complex (CPC)—a cluster of proteins that includes the kinase Aurora B—from the centromeres to the central part of the mitotic spindle, a move necessary for cytokinesis.
In the new work, Lee et al. show that Mad2 hooks up with MKlp2 early in mitosis and blocks the motor from grabbing onto the mitotic spindle. By tying up MKlp2, Mad2 halts the CPC's relocation. The team found that in cells engineered to produce extra Mad2, the CPC was stuck on centromeres. Another regulator, Cdk1, also stops MKlp2 from transporting the CPC, but the researchers discovered that the two proteins act at different points in the process. Mad2 keeps MKlp2 off the mitotic spindle, whereas Cdk1 prevents the motor from moving after it has attached to microtubules.
For mitotic cells, the payoff from Mad2’s double role might be more precise coordination between chromosome movements and cytokinesis.
