Molecular Profiling of Synaptic Vesicle Docking Sites Reveals Novel Proteins but Few Differences between Glutamatergic and GABAergic Synapses
Molecular Profiling of Synaptic Vesicle Docking Sites Reveals Novel Proteins but Few Differences between Glutamatergic and GABAergic Synapses
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DOI：
10.1016/j.neuron.2013.02.027
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发表时间：
2013-04-24
期刊：
影响因子：
16.2
通讯作者：
Chua, John Jia En
中科院分区：
文献类型：
--
作者：
Boyken, Janina;Gronborg, Mads;Chua, John Jia En
神经传递涉及钙触发的融合对接突触囊泡在专门的突触前释放网站。虽然许多参与蛋白质已被确定，这些网站的分子组成尚未得到全面的特点。在这里，我们报告了一个程序，生化分离馏分高度富集停靠突触囊泡。该部分基本上不含突触后蛋白和大多数其他细胞器，同时含有大多数已知的突触囊泡和活性区蛋白。许多突触前跨膜蛋白也被确定，连同超过30个未表征的蛋白质，其中许多是进化保守的。定量蛋白质组学比较谷氨酸和GABA-特定的对接复合物显示，除了神经递质特异性酶和转运蛋白，只有少数蛋白质选择性地富集在任一馏分。我们的结论是，参与囊泡对接和胞吐的核心机制并没有表现出两种类型的突触之间的组成差异。
Neurotransmission involves calcium-triggered fusion of docked synaptic vesicles at specialized presynaptic release sites. While many of the participating proteins have been identified, the molecular composition of these sites has not been characterized comprehensively. Here, we report a procedure to biochemically isolate fractions highly enriched in docked synaptic vesicles. The fraction is largely free of postsynaptic proteins and most other organelles while containing most known synaptic vesicle and active zone proteins. Numerous presynaptic transmembrane proteins were also identified, together with over 30 uncharacterized proteins, many of which are evolutionarily conserved. Quantitative proteomic comparison of glutamate- and GABA-specific docking complexes revealed that, except of neurotransmitter-specific enzymes and transporters, only few proteins were selectively enriched in either fraction. We conclude that the core machinery involved in vesicle docking and exocytosis does not show compositional differences between the two types of synapses.