Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
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.
- Publikationsart
- Zeitschriftenbeiträge (peer-reviewed)
- Titel
- Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles
- Medien
- Nature
- DOI
- 10.1038/22768
- Band
- 400
- Autoren
- Iris Augustin , Christian Rosenmund, Thomas C. Südhof, Nils Brose
- Seiten
- 457-461
- Veröffentlichungsdatum
- 29.07.1999
- Zitation
- Augustin, Iris; Rosenmund, Christian; Südhof, Thomas C.; Brose, Nils (1999): Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400, 457-461. DOI: 10.1038/22768