The reserve pool of synaptic vesicles acts as a buffer for proteins involved in synaptic vesicle recycling

Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):17183-8. doi: 10.1073/pnas.1112690108. Epub 2011 Sep 8.


Presynaptic nerve terminals contain between several hundred vesicles (for example in small CNS synapses) and several tens of thousands (as in neuromuscular junctions). Although it has long been assumed that such high numbers of vesicles are required to sustain neurotransmission during conditions of high demand, we found that activity in vivo requires the recycling of only a few percent of the vesicles. However, the maintenance of large amounts of reserve vesicles in many evolutionarily distinct species suggests that they are relevant for synaptic function. We suggest here that these vesicles constitute buffers for soluble accessory proteins involved in vesicle recycling, preventing their loss into the axon. Supporting this hypothesis, we found that vesicle clusters contain a large variety of proteins needed for vesicle recycling, but without an obvious function within the clusters. Disrupting the clusters by application of black widow spider venom resulted in the diffusion of numerous soluble proteins into the axons. Prolonged stimulation and ionomycin application had a similar effect, suggesting that calcium influx causes the unbinding of soluble proteins from vesicles. Confirming this hypothesis, we found that isolated synaptic vesicles in vitro sequestered soluble proteins from the cytosol in a process that was inhibited by calcium addition. We conclude that the reserve vesicles support neurotransmission indirectly, ensuring that soluble recycling proteins are delivered upon demand during synaptic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Buffers
  • Calcium / metabolism
  • Calcium / pharmacology
  • In Vitro Techniques
  • Mice
  • Models, Neurological
  • Nerve Tissue Proteins / physiology*
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiology
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology
  • Rats
  • Solubility
  • Spider Venoms / toxicity
  • Synapsins / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / physiology*


  • Buffers
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Spider Venoms
  • Synapsins
  • Calcium
  • black widow spider venom