"There were no components of this paper that were previously unknown," says Marc W. Kirschner, Carl W. Walter professor of cell biology at Harvard Medical School. "We didn't discover any new molecules." His group, however, did show how Cdc42 and PI(4,5)P2, which facilitate signals across the cell membrane, interact with N-WASP, an integrator of this signal, and with the Arp2/3 complex, to induce actin assembly.
Using Xenopus egg extracts in vitro, Kirschner and his colleagues reproduced the connections between these molecules with purified components, clearly illustrating their direct linkage biochemically. Their model suggests that Cdc42 and PI(4,5)P2 activate N-WASP, which terminates the signal by folding back on, and inhibiting, itself. "It's sort of a switch," explains Kirschner. "It can open up just like a jackknife and reveal the site that activates actin polymerization." According to Kirschner, the idea of such a self-inhibiting complex came from the work of a group ...
