A common molecular basis for membrane docking and functional priming of synaptic vesicles

Eur J Neurosci. 2009 Jul;30(1):49-56. doi: 10.1111/j.1460-9568.2009.06811.x. Epub 2009 Jun 25.


Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes execute synaptic vesicle (SV) fusion. Vesicle fusion is preceded by an obligatory Munc13-dependent priming process that conveys fusion competence to SVs by facilitating SNARE complex assembly. Ultrastructural studies after chemical fixation indicated that vesicle docking to the plasma membrane is independent of Munc13s but these results may be misleading because aldehyde fixatives modify the localization of SVs with respect to the plasma membrane. To reinvestigate the role of Munc13s in vesicle docking, cultured hippocampal slices were immobilized using high-pressure freezing, which circumvents aldehyde artifacts. High-pressure freezing was combined with electron tomography to reach a resolution that allows the characterization of details of SV docking in a close-to-native state. In control slices, docked vesicles are not hemifused with the plasma membrane but linked to it and to dense material at the active zone by small strands. In slice cultures from Munc13-deficient mice, vesicles are not docked to the active zone plasma membrane. These results indicate that SV docking at the plasma membrane and functional priming are respective morphological and physiological manifestations of the same molecular process mediated by SNARE complexes and Munc13s.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / physiology*
  • Cell Membrane / ultrastructure
  • Cytoskeletal Proteins / metabolism
  • Electron Microscope Tomography
  • Freezing
  • Hippocampus / physiology
  • Hippocampus / ultrastructure
  • Imaging, Three-Dimensional
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Pressure
  • Presynaptic Terminals / physiology*
  • Presynaptic Terminals / ultrastructure
  • Synapses / physiology
  • Synapses / ultrastructure
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure


  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Unc13a protein, mouse
  • Unc13b protein, mouse