ADF/cofilin-mediated Actin Dynamics Regulate AMPA Receptor Trafficking During Synaptic Plasticity

Nat Neurosci. 2010 Oct;13(10):1208-15. doi: 10.1038/nn.2634. Epub 2010 Sep 12.

Abstract

Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity, in which the actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins are important. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology but can also enhance synaptic potentiation in some cases. Thus, ADF/cofilin may have distinct effects on postsynaptic structure and function. We found that ADF/cofilin-mediated actin dynamics regulated AMPA receptor (AMPAR) trafficking during synaptic potentiation, which was distinct from actin's structural role in spine morphology. Specifically, elevated ADF/cofilin activity markedly enhanced surface addition of AMPARs after chemically induced long-term potentiation (LTP), whereas inhibition of ADF/cofilin abolished AMPAR addition. We found that chemically induced LTP elicited a temporal sequence of ADF/cofilin dephosphorylation and phosphorylation that underlies AMPAR trafficking and spine enlargement. These findings suggest that temporally regulated ADF/cofilin activities function in postsynaptic modifications of receptor number and spine size during synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / physiology*
  • Actins / metabolism*
  • Animals
  • Biophysics
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cells, Cultured
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electric Stimulation / methods
  • Embryo, Mammalian
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Green Fluorescent Proteins / genetics
  • Hippocampus / cytology
  • Humans
  • Hydrogen-Ion Concentration
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology*
  • Luminescent Proteins / genetics
  • Neurons / cytology
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Potassium Channel Blockers / pharmacology
  • Pregnancy
  • Protein Transport / genetics
  • Rats
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Synapses / genetics
  • Synapses / physiology*
  • Tetraethylammonium / pharmacology
  • Thiazolidines / pharmacology
  • Time Factors
  • Transfection / methods

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Excitatory Amino Acid Antagonists
  • Luminescent Proteins
  • Potassium Channel Blockers
  • Receptors, AMPA
  • Thiazolidines
  • red fluorescent protein
  • Green Fluorescent Proteins
  • Tetraethylammonium
  • latrunculin A
  • glutamate receptor ionotropic, AMPA 1