Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming
Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming
复制标题
DOI：
10.1073/pnas.122623799
复制
发表时间：
2002-06-25
影响因子：
11.1
通讯作者：
Rosenmund, C
中科院分区：
文献类型：
--
作者：
Varoqueaux, F;Sigler, A;Rosenmund, C
突触囊泡必须引发融合能力，然后才能与质膜融合，以响应增加的细胞内Ca 2+水平。突触前活性区蛋白Munc 13 -1是海马神经元中突触能突触囊泡启动所必需的。然而，在任何给定的谷氨酸能神经细胞中的一小部分突触以及所有的γ-氨基丁酸能（GABA能）突触在很大程度上独立于Munc 13 -1。我们在这里表明，Munc 13 -2，唯一的Muncl 3亚型与Munc 13 -1在海马共表达，是负责Munc 13 -1独立的海马突触囊泡启动。缺乏Munc 13 -1和Munc 13 -2的神经元既不显示诱发释放事件，也不显示自发释放事件，但形成具有典型超微结构特征的正常数目的突触。因此，两种Munc 13同种型在GABA能细胞中是完全多余的，而谷氨酸能神经元形成两种类型的突触，其中一种仅依赖于Munc 13 -1而缺乏Munc 13 -2，而另一种类型使用Munc 13 -2作为引发因子。我们的结论是，Munc 13介导的囊泡启动不是一个特定的现象，而是一个普遍的和基本的功能，多个快速的神经递质系统，突触发育过程中是不依赖于突触分泌活动。
Synaptic vesicles must be primed to fusion competence before they can fuse with the plasma membrane in response to increased intracellular Ca2+ levels. The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons. However, a small subpopulation of synapses in any given glutamatergic nerve cell as well as all gamma-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1. We show here that Munc13-2, the only Muncl 3 isoform coexpressed with Munc13-1 in hippocampus, is responsible for vesicle priming in Munc13-1 independent hippocampal synapses. Neurons lacking both Munc13-1 and Munc13-2 show neither evoked nor spontaneous release events, yet form normal numbers of synapses with typical ultrastructural features. Thus, the two Munc13 isoforms are completely redundant in GABAergic cells whereas glutamatergic neurons form two types of synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas the other type employs Munc13-2 as priming factor. We conclude that Munc13-mediated vesicle priming is not a transmitter specific phenomenon but rather a general and essential feature of multiple fast neurotransmitter systems, and that synaptogenesis during development is not dependent on synaptic secretory activity.