“Kiss-shrink-run” unifies mechanisms for synaptic vesicle exocytosis and hyperfast recycling

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-10-16 DOI:10.1126/science.ads7954

Chang-Lu Tao, Chong-Li Tian, Yun-Tao Liu, Zhen-Hang Lu, Lei Qi, Xiao-Wei Li, Chao Li, Xuefeng Shen, Min-Ling Gu, Wen-Lan Huang, Shuo Liu, Lei-Qing Yang, Zhenghan Liao, Xiaomin Ma, Jing Wu, Jianyuan Sun, Peiyi Wang, Pak-Ming Lau, Z. Hong Zhou, Guo-Qiang Bi

{"title":"“Kiss-shrink-run” unifies mechanisms for synaptic vesicle exocytosis and hyperfast recycling","authors":"Chang-Lu Tao, Chong-Li Tian, Yun-Tao Liu, Zhen-Hang Lu, Lei Qi, Xiao-Wei Li, Chao Li, Xuefeng Shen, Min-Ling Gu, Wen-Lan Huang, Shuo Liu, Lei-Qing Yang, Zhenghan Liao, Xiaomin Ma, Jing Wu, Jianyuan Sun, Peiyi Wang, Pak-Ming Lau, Z. Hong Zhou, Guo-Qiang Bi","doi":"10.1126/science.ads7954","DOIUrl":null,"url":null,"abstract":"<div >Synaptic vesicle (SV) exocytosis underpins neuronal communication, yet its nanoscale dynamics remain poorly understood owing to limitations in visualizing rapid events in situ. Here, we used optogenetics-coupled, time-resolved cryo–electron tomography to capture SV exocytosis in rat hippocampal synapses. Within 4 milliseconds of synaptic activation, SVs transiently “kiss” the plasma membrane, forming a ~4-nanometer lipidic fusion pore flanked by putative soluble NSF-attachment protein receptor (SNARE) complexes and then rapidly “shrink” to approximately half of their original surface area. By 70 milliseconds, most shrunken SVs recycle via a “run-away” pathway, whereas others collapse into the presynaptic membrane. Ultrafast endocytosis retrieves the expanded presynaptic membrane after 100 milliseconds. These findings reveal a “kiss-shrink-run” mechanism of SV exocytosis and hyperfast recycling, reconciling conflicting models and elucidating the efficiency and fidelity of synaptic transmission.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":"390 6770","pages":""},"PeriodicalIF":45.8000,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.ads7954","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Synaptic vesicle (SV) exocytosis underpins neuronal communication, yet its nanoscale dynamics remain poorly understood owing to limitations in visualizing rapid events in situ. Here, we used optogenetics-coupled, time-resolved cryo–electron tomography to capture SV exocytosis in rat hippocampal synapses. Within 4 milliseconds of synaptic activation, SVs transiently “kiss” the plasma membrane, forming a ~4-nanometer lipidic fusion pore flanked by putative soluble NSF-attachment protein receptor (SNARE) complexes and then rapidly “shrink” to approximately half of their original surface area. By 70 milliseconds, most shrunken SVs recycle via a “run-away” pathway, whereas others collapse into the presynaptic membrane. Ultrafast endocytosis retrieves the expanded presynaptic membrane after 100 milliseconds. These findings reveal a “kiss-shrink-run” mechanism of SV exocytosis and hyperfast recycling, reconciling conflicting models and elucidating the efficiency and fidelity of synaptic transmission.

Abstract Image

查看原文本刊更多论文

“吻-缩-跑”结合了突触囊泡胞吐和超高速循环的机制

突触囊泡（SV）胞外分泌是神经元通讯的基础，但由于原位快速事件的可视化限制，其纳米级动力学仍然知之甚少。在这里，我们使用光遗传学耦合，时间分辨低温电子断层扫描捕捉大鼠海马突触的SV胞分泌。在突触激活的4毫秒内，SVs瞬间“亲吻”质膜，形成一个约4纳米的脂质融合孔，两侧是假定的可溶性nsf附着蛋白受体（SNARE）复合物，然后迅速“收缩”到其原始表面积的大约一半。在70毫秒内，大多数收缩的sv通过“逃跑”途径循环，而其他sv则塌陷到突触前膜中。超快内吞作用在100毫秒后恢复扩张的突触前膜。这些发现揭示了SV胞吐和超高速循环的“亲吻-收缩-运行”机制，调和了相互矛盾的模型，并阐明了突触传递的效率和保真度。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

期刊介绍： Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.