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

Iris Augustin, Christian Rosenmund, Thomas C. Südhof and Nils Brose ()
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Iris Augustin: Max-Planck-Institut für Experimentelle Medizin, AG Molekulare Neurobiologie
Christian Rosenmund: Max-Planck-Institut fr Biophysikalische Chemie
Thomas C. Südhof: Center for Basic Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center
Nils Brose: Max-Planck-Institut für Experimentelle Medizin, AG Molekulare Neurobiologie

Nature, 1999, vol. 400, issue 6743, 457-461

Abstract: Abstract Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles1. Before fusion, vesicles dock at the presynaptic release site where they mature to a fusion-competent state1,2. Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor3,4, 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 α-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 (γ-aminobutyric acid)-containing neurons are unaffected by Munc13-1 loss, demonstrating the existence of multiple and transmitter-specific synaptic vesicle maturation processes in synapses.

Date: 1999
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DOI: 10.1038/22768

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