Cytoskeletal social networking in the growth cone: How +TIPs mediate microtubule-actin cross-linking to drive axon outgrowth and guidance

The growth cone is a unique structure capable of guiding axons to their proper destinations. Within the growth cone, extracellular guidance cues are interpreted and then transduced into physical changes in the actin filament (F-actin) and microtubule cytoskeletons, providing direction and movement. While both cytoskeletal networks individually possess important growth cone-specific functions, recent data over the past several years point towards a more cooperative role between the two systems. Facilitating this interaction between F-actin and microtubules, microtubule plus-end tracking proteins (+TIPs) have been shown to link the two cytoskeletons together. Evidence suggests that many +TIPs can couple microtubules to F-actin dynamics, supporting both microtubule advance and retraction in the growth cone periphery. In addition, growing in vitro and in vivo data support a secondary role for +TIPs in which they may participate as F-actin nucleators, thus directly influencing F-actin dynamics and organization. This review focuses on how +TIPs may link F-actin and microtubules together in the growth cone, and how these interactions may influence axon guidance. © 2016 Wiley Periodicals, Inc.