Ca2+ induces macropinocytosis via F-actin depolymerization during growth cone collapse

Mol Cell Neurosci. 2009 Jan;40(1):27-38. doi: 10.1016/j.mcn.2008.08.009. Epub 2008 Sep 11.


Growth cone collapse occurs in repulsive axon guidance and is accompanied by a reduction in the surface area of the plasma membrane of growth cones. However, the mechanism of this reduction is unclear. Here, we show that during growth cone collapse, caffeine-induced Ca(2+) release from ryanodine-sensitive Ca(2+) stores triggers the formation of large vacuoles in growth cones by macropinocytosis, a clathrin-independent endocytosis for the massive retrieval of the cellular plasma membrane, and subsequent retrograde membrane transport. We observed a significant correlation of the area of caffeine-induced macropinosomes with growth cone collapse. We also detected macropinocytosis induced by semaphorin 3A, a typical repulsive cue, and correlation between the area of semaphorin 3A-induced macropinocytic vacuoles and growth cone collapse. Moreover, jasplakinolide, an inhibitor of F-actin depolymerization, blocked caffeine-induced macropinocytosis. We propose that the coordinated regulation of actin cytoskeletal reorganization and macropinocytosis-mediated retrograde membrane trafficking may contribute to Ca(2+)-induced axon growth inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Cattle
  • Central Nervous System Stimulants / pharmacology
  • Chelating Agents / metabolism
  • Chick Embryo
  • Dextrans / chemistry
  • Dextrans / metabolism
  • Egtazic Acid / metabolism
  • Ganglia, Spinal / cytology
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Humans
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pinocytosis / physiology*
  • Ryanodine / pharmacology
  • Semaphorin-3A / metabolism
  • Serum Albumin, Bovine / metabolism
  • Statistics as Topic
  • Vacuoles / metabolism


  • Actins
  • Central Nervous System Stimulants
  • Chelating Agents
  • Dextrans
  • Semaphorin-3A
  • Ryanodine
  • Serum Albumin, Bovine
  • Caffeine
  • Egtazic Acid
  • Calcium