Departments of Neuroscience and Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration and Repair, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT, 06510, USA.
Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
Nat Commun. 2021 Jan 11;12(1):263. doi: 10.1038/s41467-020-20462-z.
Clusters of tightly packed synaptic vesicles (SVs) are a defining feature of nerve terminals. While SVs are mobile within the clusters, the clusters have no boundaries consistent with a liquid phase. We previously found that purified synapsin, a peripheral SV protein, can assemble into liquid condensates and trap liposomes into them. How this finding relates to the physiological formation of SV clusters in living cells remains unclear. Here, we report that synapsin alone, when expressed in fibroblasts, has a diffuse cytosolic distribution. However, when expressed together with synaptophysin, an integral SV membrane protein previously shown to be localized on small synaptic-like microvesicles when expressed in non-neuronal cells, is sufficient to organize such vesicles in clusters highly reminiscent of SV clusters and with liquid-like properties. This minimal reconstitution system can be a powerful model to gain mechanistic insight into the assembly of structures which are of fundamental importance in synaptic transmission.
紧密堆积的突触小泡 (SV) 簇是神经末梢的一个显著特征。虽然 SV 在簇内是可移动的，但簇没有与液相一致的边界。我们之前发现，纯化的突触相关蛋白聚糖 (synapsin)，一种外周 SV 蛋白，可以组装成液相凝聚物，并将脂质体捕获到其中。这一发现与活细胞中 SV 簇的生理形成有何关系尚不清楚。在这里，我们报告说，单独表达在成纤维细胞中的 synapsin 具有弥散的胞质分布。然而，当与突触小体蛋白 (synaptophysin) 一起表达时，这种整合的 SV 膜蛋白以前在非神经元细胞中表达时被定位在小突触样微囊泡上，足以将这些囊泡组织成类似于 SV 簇的簇，具有液态特性。这个最小的重建系统可以成为一个强大的模型，深入了解在突触传递中具有重要意义的结构的组装机制。
