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bioRxiv · 10.1101/2023.05.12.540562

Cryo-electron tomography reveals postsynaptic nanoblocks in excitatory synapses for transcellular alignment

Sun, R.·Wilson, L.·Haider, M.·Alten, B.·Zhou, Z.·Wang, X.·Zhou, Q.
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Abstract

The nanoscale organization of proteins within synapses is critical for maintaining and regulating synaptic transmission and plasticity. Here, we use cryogenic electron tomography to directly visualize the three-dimensional architecture and supramolecular organization of pre-cleft-postsynaptic components in their near-native cellular context in both synaptosomes from rat hippocampi and synapses from rat primary cultured neurons. High-resolution electron microscopy and quantitative analyses revealed that postsynaptic density (PSD) is composed of membrane-associated nanoblocks of various sizes, which are in close relationship with potential presynaptic release sites through adhesion molecules spanning the synaptic cleft, as well as with post-synaptic receptors. Subtomogram averaging from synaptosomes showed two distinct types of postsynaptic membrane proteins at resolutions of 24 [A] and 26 [A] respectively. Furthermore, our data reveal that majority of potential release sites and [~]50% subtomogram averaged receptor-like particles are located within the boundary of PSD nanoblocks, while PSD nanoblocks might be redundant for neurotransmission. The results of this study provide a more comprehensive understanding of synaptic ultrastructure and suggest that PSD is composed of clustering of various nanoblocks, which likely underlies the dynamic nature of PSD to modulate synaptic strength.

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Sun, R., Wilson, L., Haider, M., Alten, B., Zhou, Z., Wang, X., Zhou, Q.. 2023-05-13. Cryo-electron tomography reveals postsynaptic nanoblocks in excitatory synapses for transcellular alignment. https://doi.org/10.1101/2023.05.12.540562

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