Dual pools of actin at presynaptic terminals

J Neurophysiol. 2012 Jun;107(12):3479-92. doi: 10.1152/jn.00789.2011. Epub 2012 Mar 28.


We investigated actin's function in vesicle recycling and exocytosis at lamprey synapses and show that FM1-43 puncta and phalloidin-labeled filamentous actin (F-actin) structures are colocalized, yet recycling vesicles are not contained within F-actin clusters. Additionally, phalloidin also labels a plasma membrane-associated cortical actin. Injection of fluorescent G-actin revealed activity-independent dynamic actin incorporation into presynaptic synaptic vesicle clusters but not into cortical actin. Latrunculin-A, which sequesters G-actin, dispersed vesicle-associated actin structures and prevented subsequent labeled G-actin and phalloidin accumulation at presynaptic puncta, yet cortical phalloidin labeling persisted. Dispersal of presynaptic F-actin structures by latrunculin-A did not disrupt vesicle clustering or recycling or alter the amplitude or kinetics of excitatory postsynaptic currents (EPSCs). However, it slightly enhanced release during repetitive stimulation. While dispersal of presynaptic actin puncta with latrunculin-A failed to disperse synaptic vesicles or inhibit synaptic transmission, presynaptic phalloidin injection blocked exocytosis and reduced endocytosis measured by action potential-evoked FM1-43 staining. Furthermore, phalloidin stabilization of only cortical actin following pretreatment with latrunculin-A was sufficient to inhibit synaptic transmission. Conversely, treatment of axons with jasplakinolide, which induces F-actin accumulation but disrupts F-actin structures in vivo, resulted in increased synaptic transmission accompanied by a loss of phalloidin labeling of cortical actin but no loss of actin labeling within vesicle clusters. Marked synaptic deficits seen with phalloidin stabilization of cortical F-actin, in contrast to the minimal effects of disruption of a synaptic vesicle-associated F-actin, led us to conclude that two structurally and functionally distinct pools of actin exist at presynaptic sites.

Publication types

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

MeSH terms

  • Actins / analysis
  • Actins / metabolism
  • Actins / physiology*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Depsipeptides / pharmacology
  • Endocytosis / drug effects
  • Endocytosis / physiology
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Lampreys
  • Phalloidine / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Pyridinium Compounds / analysis
  • Quaternary Ammonium Compounds / analysis
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology*
  • Thiazolidines / pharmacology


  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • Depsipeptides
  • FM1 43
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Thiazolidines
  • jasplakinolide
  • Phalloidine
  • latrunculin A