该团队利用光遗传学耦合、时间分辨低温电子断层成像技术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纳米的脂质离子孔，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。
据了解，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。
附：英文原文
Title: “Kiss-shrink-run” unifies mechanisms for synaptic vesicle exocytosis and hyperfast recycling
Author: 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
Issue&Volume: 2025-10-16
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.
DOI: ads7954
Source: https://www.science.org/doi/10.1126/science.ads7954