Variability in the Munc13-1 content of excitatory release sites.
Variability in the Munc13-1 content of excitatory release sites.
复制标题
兴奋性释放位点Munc 13 -1含量的变异性。
DOI：
10.7554/elife.67468
复制
发表时间：
2021-04-27
期刊：
影响因子：
7.7
通讯作者：
Nusser Z
中科院分区：
文献类型：
--
作者：
Karlocai MR;Heredi J;Benedek T;Holderith N;Lorincz A;Nusser Z
皮层谷氨酸能突触多样性的分子机制尚不完全清楚。在这里，我们验证了突触前活跃区（AZs）由分子均匀的独立释放位点（RSs）构成的假设，其数量与AZ大小成线性关系。在成年小鼠的急性切片中，海马CA1锥体细胞和快速尖峰中间神经元之间的配对记录以及随后的定量分析表明，这些连接处的RSs (N)数量存在很大差异。功能特征突触的高分辨率分子分析揭示了具有相同n的az中关键囊泡启动因子之一Munc13-1含量的变变性。复制免疫标记还显示，相同大小的az中Munc13-1总含量的变变性为3倍，而az内Munc13-1簇的大小和密度的变变性为4倍。我们的研究结果为RSs的定量分子异质性提供了证据，并支持了AZ由不同数量的分子异质性但独立的RSs建立的模型。
The molecular mechanisms underlying the diversity of cortical glutamatergic synapses are still incompletely understood. Here, we tested the hypothesis that presynaptic active zones (AZs) are constructed from molecularly uniform, independent release sites (RSs), the number of which scales linearly with the AZ size. Paired recordings between hippocampal CA1 pyramidal cells and fast-spiking interneurons in acute slices from adult mice followed by quantal analysis demonstrate large variability in the number of RSs (N) at these connections. High-resolution molecular analysis of functionally characterized synapses reveals variability in the content of one of the key vesicle priming factors – Munc13-1 – in AZs that possess the same N. Replica immunolabeling also shows a threefold variability in the total Munc13-1 content of AZs of identical size and a fourfold variability in the size and density of Munc13-1 clusters within the AZs. Our results provide evidence for quantitative molecular heterogeneity of RSs and support a model in which the AZ is built up from variable numbers of molecularly heterogeneous, but independent RSs.