Putting the brakes on a molecular motor might help cells fashion the mitotic spindle, Ma et al. report.
The protein TPX2 performs several jobs during spindle construction. For instance, it activates and positions Aurora A, a kinase necessary for spindle formation. TPX2 also latches onto the molecular motor Eg5, which crosslinks microtubules and pulls them past each other. Early in mitosis, Eg5 produces outward forces that push the spindle poles apart. Ma et al. wanted to determine how the interaction between TPX2 and Eg5 affects mitosis.
The researchers outfitted cells with a bacterial artificial chromosome encoding a version of TPX2 lacking the region that connects to Eg5. Then they used RNAi to deplete the cells' own version of TPX2. The cells made jumbled spindles with multiple poles and bowed microtubules. Thwarting the interaction between Eg5 and TPX2 caused another problem—the cells didn't make the kinetochore microtubules that attach to chromosomes and tug them apart.
Ma et al. found that TPX2 helps Eg5 to settle on the spindle microtubules between the poles. TPX2 also reduces the motor's ability to slide microtubules past one another in the spindle. The researchers hypothesize that, by idling the motor protein, TPX2 prevents it from generating too much outward force, which would lead to multiple poles or distorted fibers. One mystery, the researchers say, is how the interaction between TPX2 and Eg5 promotes stable connections between kinetochores and the spindle.
