Vesicle fusion at preestablished plasma membrane release sites releases transmitters and hormones to mediate fundamental functions like neuronal network activities and fight-or-flight responses. This half-a-century-old concept—fusion at well-established release sites in excitable cells—needs to be modified to include the sequential compound fusion reported here—vesicle fusion at previously fused Ω-shaped vesicular membrane. With superresolution STED microscopy in excitable neuroendocrine chromaffin cells, we real-time visualized sequential compound fusion pore openings and content releases in generating multivesicular and asynchronous release from single release sites, which enhances exocytosis strength and dynamic ranges in excitable cells. We also visualized subsequent compound fusion pore closure, a new mode of endocytosis termed compound kiss-and-run that enhances vesicle recycling capacity. These results suggest modifying current exo-endocytosis concepts by including rapid release-site assembly at fused vesicle membrane, where sequential compound fusion and kiss-and-run take place to enhance exo-endocytosis capacity and dynamic ranges.

中文翻译：

---

顺序复合融合和接吻运行介导可兴奋细胞的外吞和内吞作用

预先建立的质膜释放位点的囊泡融合释放递质和激素，以调节神经元网络活动和战或逃反应等基本功能。这个有半个世纪历史的概念——在可兴奋细胞中确定的释放位点融合——需要修改以包括这里报道的顺序复合融合——在先前融合的 Ω 形囊泡膜上的囊泡融合。通过在可兴奋的神经内分泌嗜铬细胞中使用超分辨率 STED 显微镜，我们实时可视化连续复合融合孔开口和内容物释放，从而从单个释放位点产生多泡和异步释放，从而增强可兴奋细胞的胞吐强度和动态范围。我们还可视化了随后的复合融合孔隙闭合，一种新的内吞模式称为复合接吻运行，可增强囊泡回收能力。这些结果表明通过在融合囊泡膜处包括快速释放位点组装来修改当前的外吞作用概念，其中发生顺序复合融合和接吻运行以增强外吞作用能力和动态范围。