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Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission.
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.celrep.2019.12.035 Maria Jäpel 1 , Fabian Gerth 2 , Takeshi Sakaba 3 , Jelena Bacetic 4 , Lijun Yao 5 , Seong-Joo Koo 1 , Tanja Maritzen 1 , Christian Freund 2 , Volker Haucke 6
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.celrep.2019.12.035 Maria Jäpel 1 , Fabian Gerth 2 , Takeshi Sakaba 3 , Jelena Bacetic 4 , Lijun Yao 5 , Seong-Joo Koo 1 , Tanja Maritzen 1 , Christian Freund 2 , Volker Haucke 6
Affiliation
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The rapid replenishment of release-ready synaptic vesicles (SVs) at a limiting number of presynaptic release sites is required to sustain high-frequency neurotransmission in CNS neurons. Failure to clear release sites from previously exocytosed material has been shown to impair vesicle replenishment and, therefore, fast neurotransmission. The identity of this material and the machinery that removes it from release sites have remained enigmatic. Here we show that the endocytic scaffold protein intersectin 1 clears release sites by direct SH3 domain-mediated association with a non-canonical proline-rich segment of synaptobrevin assembled into the SNARE complex for neuroexocytosis. Acute structure-based or sustained genetic interference with SNARE complex recognition by intersectin 1 causes a rapid stimulation frequency-dependent depression of neurotransmission due to impaired replenishment of release-ready SVs. These findings identify a key molecular mechanism that underlies exo-endocytic coupling during fast neurotransmitter release at central synapses.
中文翻译：
快速神经传递需要Intersectin介导的SNARE配合物清除。
为了维持中枢神经系统神经元的高频神经传递，需要在有限数量的突触前释放位点快速补充准备就绪的突触囊泡（SVs）。已显示未能清除先前胞吐物质的释放位点会损害囊泡的补充，因此会导致快速的神经传递。这种材料的身份以及将其从释放地点移出的机器仍然难以捉摸。在这里，我们显示内吞的支架蛋白intersectin 1通过直接SH3域介导的与突触短纤维蛋白的非规范性脯氨酸丰富的节段组装成SNARE复合物的神经外排作用的直接SH3域介导的关联来清除释放位点。Intersectin 1对SNARE复杂识别的基于急性结构的或持续的遗传干扰，由于释放准备就绪的SV的补给受损，导致神经传递的快速刺激频率依赖性抑制。这些发现确定了关键的分子机制，其是中枢突触快速神经递质释放过程中外-内吞偶联的基础。
更新日期：2020-01-15
中文翻译：
快速神经传递需要Intersectin介导的SNARE配合物清除。
为了维持中枢神经系统神经元的高频神经传递，需要在有限数量的突触前释放位点快速补充准备就绪的突触囊泡（SVs）。已显示未能清除先前胞吐物质的释放位点会损害囊泡的补充，因此会导致快速的神经传递。这种材料的身份以及将其从释放地点移出的机器仍然难以捉摸。在这里，我们显示内吞的支架蛋白intersectin 1通过直接SH3域介导的与突触短纤维蛋白的非规范性脯氨酸丰富的节段组装成SNARE复合物的神经外排作用的直接SH3域介导的关联来清除释放位点。Intersectin 1对SNARE复杂识别的基于急性结构的或持续的遗传干扰，由于释放准备就绪的SV的补给受损，导致神经传递的快速刺激频率依赖性抑制。这些发现确定了关键的分子机制，其是中枢突触快速神经递质释放过程中外-内吞偶联的基础。
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