Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles
1999 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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- Authors
- Augustin, Iris; Rosenmund, C.; Suedhof, Thomas C.; Brose, Nils
- Abstract
- 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(1,2). Here we identify Munc13-1, a brain-specific presynaptic phorbol ester receptor(3,4), 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 alpha-latrotolrin 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.
- Issue Date
- 1999
- Publisher
- Macmillan Magazines Ltd
- Journal
- Nature
- ISSN
- 0028-0836