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¹ Department of Anatomy and Cell Biology, University at Buffalo, SUNY, Buffalo, NY 14214
² Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Dr. Christopher S. Cohan, Department of Anatomy and Cell Biology, University at Buffalo, Buffalo, NY 14214. Tel.: (716) 829-3081. Fax: (716) 829-2911. E-mail: ccohan{at}buffalo.edu

Ît is commonly believed that growth cone turning during pathfinding is initiated by reorganization of actin filaments in response to guidance cues, which then affects microtubule structure to complete the turning process. However, a major unanswered question is how changes in actin cytoskeleton are induced by guidance cues and how these changes are then translated into microtubule rearrangement. Here, we report that local and specific disruption of actin bundles from the growth cone peripheral domain induced repulsive growth cone turning. Meanwhile, dynamic microtubules within the peripheral domain were oriented into areas where actin bundles remained and were lost from areas where actin bundles disappeared. This resulted in directional microtubule extension leading to axon bending and growth cone turning. In addition, this local actin bundle loss coincided with localized growth cone collapse, as well as asymmetrical lamellipodial protrusion. Our results provide direct evidence, for the first time, that regional actin bundle reorganization can steer the growth cone by coordinating actin reorganization with microtubule dynamics. This suggests that actin bundles can be potential targets of signaling pathways downstream of guidance cues, providing a mechanism for coupling changes in leading edge actin with microtubules at the central domain during turning.

Key Words: axon guidance; pathfinding; actin bundles; cytoskeleton; microtubules

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