Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles
Munc13-1 is essential for fusion competence of glutamatergic synoptic vesicles
复制标题
作者：
Augustin, I;Rosenmund, C;Brose, N
神经细胞间突触的神经递质释放是由钙触发的突触囊泡胞外融合介导的。在融合之前，囊泡停靠在突触前释放位点，在那里它们成熟到融合能力状态（1,2）。在这里，我们发现Munc13-1，一种脑特异性突触前酚酯受体（3,4），是突触囊泡成熟的必需蛋白。我们发现缺乏Munc13-1的小鼠的谷氨酸能海马神经元形成超微结构正常的突触，其突触-囊泡周期在成熟阶段被阻止。从突变突触释放的递质不能被动作电位、钙离子载体或高渗蔗糖溶液触发。相比之下，α - latotolrin引发的释放与野生型对照没有区别，表明该毒素可以绕过munc13 -1介导的囊泡成熟。任何给定的谷氨酸能神经元的一小部分突触以及所有含GABA （γ -氨基丁酸）的神经元的突触不受Munc13-1缺失的影响，这表明突触中存在多种和递质特异性的突触囊泡成熟过程。
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.