Arp2/3 forms short, branched actin filaments in lamellipodia to drive movement in fibroblasts. Axons, however, do not need Arp2/3 activity for forward momentum, as the authors show that axons are longer if Arp2/3 is inhibited. But these axons did not change direction in response to guidance cues. They passed straight over inhibitory signals rather than turning away.
Longer axons usually have very stable microtubules, but the long Arp2/3-less axons had overly dynamic microtubules. Their instability may impair the coordination of actin and microtubule networks that is needed for growth cone turning. “The microtubules are out of control,” says Lanier. “Like on a highway, if you go too fast, you might see the exit, which is the turning cue, but you might not respond in time.”
Arp2/3 was found at the center of growth cones rather than the periphery, where it lies in fibroblasts. A highly branched central actin network might be a physical barrier to microtubules, thus slowing their growth just enough for a timely response to actin changes. ▪