Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD, US.
Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, US.
Nat Commun. 2023 May 20;14(1):2888. doi: 10.1038/s41467-023-38595-2.
Compensatory endocytosis keeps the membrane surface area of secretory cells constant following exocytosis. At chemical synapses, clathrin-independent ultrafast endocytosis maintains such homeostasis. This endocytic pathway is temporally and spatially coupled to exocytosis; it initiates within 50 ms at the region immediately next to the active zone where vesicles fuse. However, the coupling mechanism is unknown. Here, we demonstrate that filamentous actin is organized as a ring, surrounding the active zone at mouse hippocampal synapses. Assuming the membrane area conservation is due to this actin ring, our theoretical model suggests that flattening of fused vesicles exerts lateral compression in the plasma membrane, resulting in rapid formation of endocytic pits at the border between the active zone and the surrounding actin-enriched region. Consistent with model predictions, our data show that ultrafast endocytosis requires sufficient compression by exocytosis of multiple vesicles and does not initiate when actin organization is disrupted, either pharmacologically or by ablation of the actin-binding protein Epsin1. Our work suggests that membrane mechanics underlie the rapid coupling of exocytosis to endocytosis at synapses.
胞吞作用补偿使分泌细胞的膜表面积在胞吐作用后保持恒定。在化学突触中,网格蛋白非依赖的超快胞吞作用维持这种动态平衡。这种胞吞途径在时间和空间上与胞吐作用偶联;它在紧邻融合囊泡的活性区的区域内于 50 毫秒内启动。然而,偶联机制尚不清楚。在这里,我们证明在小鼠海马突触中,丝状肌动蛋白组织成一个环,环绕在活性区周围。假设膜面积的守恒是由于这个肌动蛋白环,我们的理论模型表明,融合囊泡的扁平化在质膜中施加了侧向压缩,导致在活性区和周围富含肌动蛋白的区域之间的边界处迅速形成胞饮凹陷。与模型预测一致,我们的数据表明,超快胞吞作用需要通过多个囊泡的胞吐作用来提供足够的压缩,并且当肌动蛋白的组织被破坏时,无论是通过药理学还是通过消融肌动蛋白结合蛋白 Epsin1 ,胞吞作用都不会启动。我们的工作表明,在突触处,胞吐作用与胞吞作用的快速偶联是由膜力学决定的。
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