NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Every time a cell divides, it needs to duplicate its DNA and evenly distribute it between the two new ‘daughter’ cells. To move and distribute DNA, the cell builds a large machine called a spindle, which is made of stiff cables called microtubules. Many proteins, including a motor called dynein, help to organize the spindle’s microtubules. One of dynein’s jobs is to cluster all microtubules at the two tips of the spindle, pulling them into shape. Without this clustering, spindles have the wrong shape and structure and can make mistakes when moving DNA. Microtubules have a ‘plus’ end and a ‘minus’ end, and motor proteins usually only travel in one specified direction. Dynein, for example, moves towards the minus end of microtubules, which is where most of the clustering happens. It can form a complex with other proteins that help clustering, one of which is called NuMA. Until now, it was thought that dynein transports NuMA to the minus ends. To test this model, Hueschen et al. studied dividing human cells under a microscope and isolated minus ends with the help of a laser. The experiments showed that, in fact, NuMA gets to minus ends independently of dynein. Once it is on the minus ends, NuMA grabs hold of another protein complex called dynactin, which then gathers dynein. Dynein then pulls the spindles into shape from the minus ends. When NuMA was experimentally removed from the cells, dynein-dynactin complexes were scattered along the entire length of the microtubule instead of pulling specifically on minus-ends, which resulted in disorganized spindles. Thus, where dynein complexes pull determines what spindle shape they build. Hueschen et al. also showed that dynein complexes only pull on minus-ends while the cell divides, which makes sense, because NuMA remains hidden in the cell nucleus for the rest of the time. Together, these results suggest that NuMA makes sure dynein pulls specifically on the minus-ends of the microtubules to tighten the spindle at the right time. A next step will be to test how the mechanical properties of the spindle are changed without dynein pulling on minus-ends. A better knowledge of how different proteins work together to build the spindle and help cells divide can help us understand what goes wrong when cells divide abnormally, as in the case of cancer cells.