A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion.
A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion.
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DOI：
10.1038/ncomms6774
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发表时间：
2014-12-17
影响因子：
16.6
通讯作者：
Duncan RR
中科院分区：
文献类型：
--
作者：
Kavanagh DM;Smyth AM;Martin KJ;Dun A;Brown ER;Gordon S;Smillie KJ;Chamberlain LH;Wilson RS;Yang L;Lu W;Cousin MA;Rickman C;Duncan RR
神经元突触是最受关注的细胞系统之一，是所有膜运输研究的模型。尽管如此，由于中央突触及其内部分子的小尺寸和动态性质，突触生物学已被证明很难直接在原位进行询问。在这里，我们确定突触前蛋白的空间和时间相互作用状态，对活跃突触内的大量单分子进行成像。测量突触去极化过程中的快速相互作用动力学发现，支持突触囊泡胞吐所需的Synaxin1a和Munc18-1蛋白分子数量很少。在囊泡融合和随后的SNAR复合体分解后，在Synaxin1a和Munc18-1结合模式中的迅速切换，受Synaxin1a N端电荷变化的调节，将单体Synaxin1a从其他分解的融合复合体成分中隔离出来，防止异位SNARE复合体的形成，为随后几轮的神经传递做好准备。突触囊泡融合涉及一种被称为SNARE复合体的多蛋白组装，在空间和时间上都受到严格的调控。这里，Kavanagh等人。结果表明，在突触内囊泡融合和SNARE复合体分解后，SNARE蛋白Synaxin1a被Munc18-1以单体形式隔离，阻止了异位SNARE复合体的组装。
Neuronal synapses are among the most scrutinized of cellular systems, serving as a model for all membrane trafficking studies. Despite this, synaptic biology has proven difficult to interrogate directly in situ due to the small size and dynamic nature of central synapses and the molecules within them. Here we determine the spatial and temporal interaction status of presynaptic proteins, imaging large cohorts of single molecules inside active synapses. Measuring rapid interaction dynamics during synaptic depolarization identified the small number of syntaxin1a and munc18-1 protein molecules required to support synaptic vesicle exocytosis. After vesicle fusion and subsequent SNARE complex disassembly, a prompt switch in syntaxin1a and munc18-1-binding mode, regulated by charge alteration on the syntaxin1a N-terminal, sequesters monomeric syntaxin1a from other disassembled fusion complex components, preventing ectopic SNARE complex formation, readying the synapse for subsequent rounds of neurotransmission. Synaptic vesicle fusion involves a multi-protein assembly called the SNARE complex that is tightly regulated both spatially and temporally. Here Kavanagh et al. show that after vesicle fusion and SNARE complex disassembly in the synapse, the SNARE protein syntaxin1a is sequestered in a monomeric form by munc18-1, preventing ectopic SNARE complex assembly.
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影响因子：
5.3
作者：
Gulyas-Kovacs, Attila;de Wit, Heidi;Sorensen, Jakob B.
通讯作者：
Sorensen, Jakob B.
DOI：
10.1523/jneurosci.2337-12.2013
发表时间：
2013-03-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Degtyar V;Hafez IM;Bray C;Zucker RS
通讯作者：
Zucker RS
影响因子：
3.3
作者：
Lam, Alice D.;Tryoen-Toth, Petra;Stuenkel, Edward L.
通讯作者：
Stuenkel, Edward L.
影响因子：
11.4
作者：
Dulubova, I;Sugita, S;Rizo, J
通讯作者：
Rizo, J
DOI：
10.1073/pnas.0611318104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Dulubova, Irina;Khvotchev, Mikhail;Rizo, Josep
通讯作者：
Rizo, Josep