Second messengers and membrane trafficking direct and organize growth cone steering

Nat Rev Neurosci. 2011 Apr;12(4):191-203. doi: 10.1038/nrn2996. Epub 2011 Mar 9.


Graded distributions of extracellular cues guide developing axons toward their targets. A network of second messengers - Ca(2+) and cyclic nucleotides - shapes cue-derived information into either attractive or repulsive signals that steer growth cones bidirectionally. Emerging evidence suggests that such guidance signals create a localized imbalance between exocytosis and endocytosis, which in turn redirects membrane, adhesion and cytoskeletal components asymmetrically across the growth cone to bias the direction of axon extension. These recent advances allow us to propose a unifying model of how the growth cone translates shallow gradients of environmental information into polarized activity of the steering machinery for axon guidance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Axons / metabolism*
  • Calcium / metabolism
  • Cell Physiological Phenomena*
  • Growth Cones / physiology*
  • Models, Biological
  • Protein Transport / physiology
  • Second Messenger Systems / physiology*


  • Calcium