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

摘要: Neurotransmitter release at synapses between nerve cells is mediated by calcium-triggered exocytotic fusion of synaptic vesicles1. Before fusion, vesicles dock the presynaptic site where they mature to a fusion-competent state1,2. Here we identify Munc13-1, brain-specific phorbol ester receptor3,4, as an essential protein for vesicle maturation. We show that glutamatergic hippocampal neurons from mice lacking Munc13-1 form ultrastructurally normal whose synaptic-vesicle cycle arrested maturation step. Transmitter mutant cannot be triggered action potentials, calcium-ionophores or hypertonic sucrose solution. In contrast, evoked α-latrotoxin indistinguishable wild-type controls, indicating toxin can bypass Munc13-1-mediated A small subpopulation any given neuron well all GABA (γ-aminobutyric acid)-containing are unaffected loss, demonstrating existence multiple and transmitter-specific processes in synapses.