Details

Autor(en) / Beteiligte

• Augustin, Iris
• Rosenmund, Christian
• Südhof, Thomas C
• Brose, Nils

Titel

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

Ist Teil von

• Nature (London), 1999-07, Vol.400 (6743), p.457-461

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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.