Sun Rong, Allen James P, Mao Zhuqing, Wilson Liana, Haider Mariam, Alten Baris, Zhou Zimeng, Wang Xinyi, Zhou Qiangjun
Department of Cell and Developmental Biology, Center for Structural Biology, Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN, USA.
Vanderbilt Brain Institute, Vanderbilt University , Nashville, TN, USA.
J Cell Biol. 2025 Jun 2;224(6). doi: 10.1083/jcb.202406133. Epub 2025 Mar 27.
The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we used cryo-electron tomography (cryo-ET) to directly visualize the three-dimensional architecture and supramolecular organization of postsynaptic components in both synaptosomes and synapses from cultured neurons. Cryo-ET revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes. Subtomogram averaging from synaptosomes showed two types (type A and B) of postsynaptic receptor-like particles at resolutions of 24 and 26 Å, respectively. Furthermore, our analysis suggested that potential presynaptic release sites are closer to nanoblocks with type A/B receptor-like particles than to nanoblocks without type A/B receptor-like particles. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks. These nanoblocks are heterogeneous in size, assembly, and distribution, which likely contribute to the dynamic nature of PSD in modulating synaptic strength.
突触内蛋白质的纳米级组织对于维持和调节突触传递及可塑性至关重要。在此，我们使用冷冻电子断层扫描（cryo-ET）直接观察培养神经元的突触体和突触中突触后成分的三维结构和超分子组织。冷冻电子断层扫描显示，突触后致密区（PSD）由各种大小的膜相关纳米块组成。来自突触体的亚断层平均分析分别在24 Å和26 Å的分辨率下显示出两种类型（A型和B型）的突触后受体样颗粒。此外，我们的分析表明，潜在的突触前释放位点更靠近带有A型/ B型受体样颗粒的纳米块，而不是没有A型/ B型受体样颗粒的纳米块。本研究结果提供了对突触超微结构更全面的理解，并表明PSD由各种纳米块的聚集组成。这些纳米块在大小、组装和分布上是异质的，这可能有助于PSD在调节突触强度方面的动态性质。
