Ca(2+) influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites

Mol Cell Neurosci. 2008 Feb;37(2):261-70. doi: 10.1016/j.mcn.2007.10.001. Epub 2007 Oct 10.


In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca(2+) imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca(2+) increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca(2+) influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Actins / drug effects
  • Actins / metabolism
  • Actins / ultrastructure
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Calcineurin / metabolism
  • Calcineurin Inhibitors
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cofilin 1 / metabolism*
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Antibody Technique
  • Neurites / drug effects
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • PC12 Cells
  • Phosphorylation / drug effects
  • Rats
  • Receptors, Purinergic P2 / drug effects
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Actins
  • Calcineurin Inhibitors
  • Cfl1 protein, rat
  • Cofilin 1
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X
  • Adenosine Triphosphate
  • Calcineurin
  • Calcium