PMID- 10440375
OWN - NLM
STAT- MEDLINE
DCOM- 19990813
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6743
DP  - 1999 Jul 29
TI  - Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles.
PG  - 457-61
AB  - 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.
FAU - Augustin, I
AU  - Augustin I
AD  - Max-Planck-Institut fur Experimentelle Medizin, AG Molekulare Neurobiologie,
      Gottingen, Bundesrepublik Deutschland.
FAU - Rosenmund, C
AU  - Rosenmund C
FAU - Sudhof, T C
AU  - Sudhof TC
FAU - Brose, N
AU  - Brose N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Spider Venoms)
RN  - 0 (Unc13b protein, mouse)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 65988-34-3 (alpha-latrotoxin)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Action Potentials
MH  - Animals
MH  - Cells, Cultured
MH  - Dizocilpine Maleate/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glutamic Acid/metabolism
MH  - Hippocampus/cytology/physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Fusion/*physiology
MH  - Mice
MH  - Nerve Tissue Proteins/genetics/*physiology
MH  - Neurons/physiology/ultrastructure
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
MH  - Sequence Deletion
MH  - Spider Venoms/pharmacology
MH  - Synapses/ultrastructure
MH  - Synaptic Transmission/drug effects/*physiology
MH  - Synaptic Vesicles/*physiology/ultrastructure
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 1999/08/10 10:00
MHDA- 2000/04/01 09:00
CRDT- 1999/08/10 10:00
PHST- 1999/08/10 10:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 1999/08/10 10:00 [entrez]
AID - 10.1038/22768 [doi]
PST - ppublish
SO  - Nature. 1999 Jul 29;400(6743):457-61. doi: 10.1038/22768.