Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles

Nature. 1999 Jul 29;400(6743):457-61. doi: 10.1038/22768.


Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles. Before fusion, vesicles dock at the presynaptic release site where they mature to a fusion-competent state. Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor, as an essential protein for synaptic vesicle maturation. We show that glutamatergic hippocampal neurons from mice lacking Munc13-1 form ultrastructurally normal synapses whose synaptic-vesicle cycle is arrested at the maturation step. Transmitter release from mutant synapses cannot be triggered by action potentials, calcium-ionophores or hypertonic sucrose solution. In contrast, release evoked by alpha-latrotoxin is indistinguishable from wild-type controls, indicating that the toxin can bypass Munc13-1-mediated vesicle maturation. A small subpopulation of synapses of any given glutamatergic neuron as well as all synapses of GABA (gamma-aminobutyric acid)-containing neurons are unaffected by Munc13-1 loss, demonstrating the existence of multiple and transmitter-specific synaptic vesicle maturation processes in synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Cells, Cultured
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Fusion / physiology*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Sequence Deletion
  • Spider Venoms / pharmacology
  • Synapses / ultrastructure
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure
  • gamma-Aminobutyric Acid / metabolism


  • Excitatory Amino Acid Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Spider Venoms
  • Unc13b protein, mouse
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • alpha-latrotoxin
  • Dizocilpine Maleate