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

Cytoskeleton (Hoboken). 2016 Sep;73(9):461-76. doi: 10.1002/cm.21272. Epub 2016 Feb 8.


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.

Keywords: +TIPs; axon guidance; cytoskeleton; growth cone; microtubule dynamics.

Publication types

  • Review

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism*
  • Growth Cones / metabolism*
  • Humans
  • Microtubule Proteins / metabolism*
  • Microtubules / metabolism*
  • gamma-Aminobutyric Acid


  • Actins
  • Microtubule Proteins
  • gamma-Aminobutyric Acid