Pulling Together: Mitotic ring self-assembly revealed

During cell division, a ring of proteins forms around a cell’s “equator” and then contracts to pinch the cell in half. These proteins arrange themselves into an orderly ring by a random process of searching, grabbing, and pulling each other, scientists have discovered.

Finding this ring-forming mechanism answers a basic question of cell biology from the 1970s, when researchers learned that the ring of proteins contains actin and myosin, the same molecules that generate contractions in muscle cells.

Only recently have modern genetics, cell imaging, and computing techniques made it possible to figure out how the ring assembles itself, says Thomas D. Pollard of Yale University. He and his colleagues proposed mechanisms for how this self-assembly occurs based on microscope observations of dividing yeast cells. By flagging actin and myosin with fluorescent proteins, the researchers could see the movements of these proteins. They used this information to create simulations of the process. The team then looked at whether the movements of these proteins in real cells matched the behavior produced in the simulations. “The mechanism was tested by computer simulations at every step,” Pollard says. “It’s actually a little scary how close [the simulation is] to the real thing.”

To form the ring, approximately 60 small nodules containing myosin and other proteins first gather at the cell’s outer membrane, near the equator. As the time for cell division approaches, each nodule spawns a straight filament of actin, which extends in a random direction by rapidly tacking more units of actin on to its end.

If a filament happens to pass close to another nodule, myosin in that nodule will grab on to the filament and begin pulling, drawing the two nodules closer together.

Surprisingly, myosin in yeast cells spontaneously lets go after about 20 seconds, and the actin-sprouting nodule generates a new filament in another random direction. “It seems counterproductive,” Pollard says. “You’ve got everybody hooked up, so why don’t you just go ahead and keep on pulling?”

When the researchers tried a continuous-pulling scenario in their computer simulations, the nodules failed to form an orderly ring. Instead, they gathered into randomly spaced clumps.

Letting go and reaching out in a new direction over and over again allowed the nodules to uniformly draw together into a ring instead of merely huddling with their nearest neighbors, the researchers report online and in an upcoming Science.

“It’s truly pioneering stuff,” comments Alexander Mogilner of the University of California, Davis who has performed research on the self-organization of actin and myosin. “The insight they got is incredibly detailed and vivid.”