| First Author | Augustin I | Year | 1999 |
| Journal | Nature | Volume | 400 |
| Issue | 6743 | Pages | 457-61 |
| PubMed ID | 10440375 | Mgi Jnum | J:56513 |
| Mgi Id | MGI:1341485 | Doi | 10.1038/22768 |
| Citation | Augustin I, et al. (1999) Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 400(6743):457-61 |
| abstractText | 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. |
