The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones

Neuron. 2014 Oct 22;84(2):416-31. doi: 10.1016/j.neuron.2014.10.009. Epub 2014 Oct 22.


Synaptic vesicle docking, priming, and fusion at active zones are orchestrated by a complex molecular machinery. We employed hippocampal organotypic slice cultures from mice lacking key presynaptic proteins, cryofixation, and three-dimensional electron tomography to study the mechanism of synaptic vesicle docking in the same experimental setting, with high precision, and in a near-native state. We dissected previously indistinguishable, sequential steps in synaptic vesicle active zone recruitment (tethering) and membrane attachment (docking) and found that vesicle docking requires Munc13/CAPS family priming proteins and all three neuronal SNAREs, but not Synaptotagmin-1 or Complexins. Our data indicate that membrane-attached vesicles comprise the readily releasable pool of fusion-competent vesicles and that synaptic vesicle docking, priming, and trans-SNARE complex assembly are the respective morphological, functional, and molecular manifestations of the same process, which operates downstream of vesicle tethering by active zone components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / metabolism
  • Membrane Fusion / physiology
  • Mice
  • Neurons / metabolism
  • Neurons / ultrastructure
  • SNARE Proteins / metabolism*
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism*


  • SNARE Proteins