Loss of actin bundles (black) and microtubules (red) turns growth cones away from repulsive cues.

Tightly bundled actin filaments direct axonal pathfinding, according to new study by Zhou et al. on page 839. The results identify how changes in actin structure control microtubule polymerization during neurite growth.As a neuron extends its axon, the growth cone turns toward certain cues and away from others. Turning involves collapse of lamellipodia to avoid the inhibitory signal and growth in a different direction. Although a requirement for actin and microtubules in this process is well established, how the two cytoskeletal elements change in response to avoidance cues was not known.

Zhou et al. have determined that disassembly of actin bundles is all that is necessary to initiate axon turning. In the absence of the bundles, force generated from actin retrograde flow toward the growth cone center prevents the extension of microtubules toward the leading edge. Inhibitory cues such as collapsin probably signal from their receptors to inhibit actin-bundling proteins, such as myosin II or fascin. This results in local lamellipodial collapse and asymmetric growth away from the inhibitory signal.

Based on microscopy, it appears that microtubules use actin bundles to extend toward the lamellipodia. How the bundles allow the microtubules to overcome retrograde flow is unclear, but may involve proteins such as MAPs and plakins, which have both actin- and tubulin-binding domains. ▪