Getting ahead by staying still

Migrating cells send the nucleus backward rather than the microtubule-organizing center (MTOC) forward, say Edgar Gomes, Shantanu Jani, and Gregg Gundersen (Columbia University, New York, NY).As cells begin to migrate, they spin their internal contents around to orient in the direction of overall cell movement. Movement of a MTOC was thought to lead the way in this process. Consistent with this idea, dynein tugged on MTOCs in other settings, and was concentrated at the leading edge of moving cells. The MTOC moving toward the front of a migrating cell “had been our model forever,” says Gundersen.

The trouble is, he says, “people weren't looking early enough.” They had seen the final result but not the movement itself. Now, this team gets reorientation going with LPA before initiating migration with serum. That allows them to catch the nucleus moving backward even as the MTOC stays put.

The GTPase Cdc42 and its target MRCK were necessary and sufficient for nuclear movement. These proteins prompt actin polymerization at the front of the cell and thus actin retrograde flow, whose timing and speed match that of nuclear movement. The team favors an actin conveyor-belt model for nuclear movement, but has not ruled out a bulldozer model.

The MTOC stayed fixed in the center of the cell thanks to a group of proteins including dynein, Par6 and PKCζ; without them it wandered backward with the nucleus. How the MTOC is centered is a mystery—some have suggested that the pull of motors on microtubules is proportional to the length of the microtubules.

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