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Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density

Postsynaptic densities (PSDs) are large protein complexes associated with the postsynaptic membrane of excitatory synapses important for synaptic function including plasticity. Conventional electron microscopy (EM) typically depicts PSDs as compact disk-like structures of hundreds of nanometers in s...

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Autores principales: Jung, Jae Hoon, Chen, Xiaobing, Reese, Thomas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117989/
https://www.ncbi.nlm.nih.gov/pubmed/37091879
http://dx.doi.org/10.3389/fnsyn.2023.1123564
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author Jung, Jae Hoon
Chen, Xiaobing
Reese, Thomas S.
author_facet Jung, Jae Hoon
Chen, Xiaobing
Reese, Thomas S.
author_sort Jung, Jae Hoon
collection PubMed
description Postsynaptic densities (PSDs) are large protein complexes associated with the postsynaptic membrane of excitatory synapses important for synaptic function including plasticity. Conventional electron microscopy (EM) typically depicts PSDs as compact disk-like structures of hundreds of nanometers in size. Biochemically isolated PSDs were also similar in dimension revealing a predominance of proteins with the ability to polymerize into an extensive scaffold; several EM studies noted their irregular contours with often small granular structures (<30 nm) and holes. Super-resolution light microscopy studies observed clusters of PSD elements and their activity-induced lateral movement. Furthermore, our recent EM study on PSD fractions after sonication observed PSD fragments (40–90 nm in size) separate from intact PSDs; however, such structures within PSDs remained unidentified. Here we examined isolated PSDs by cryo-EM tomography with our new approach of automatic segmentation that enables delineation of substructures and their quantitative analysis. The delineated substructures broadly varied in size, falling behind 30 nm or exceeding 100 nm and showed that a considerable portion of the substructures (>38%) in isolated PSDs was in the same size range as those fragments. Furthermore, substructures spanning the entire thickness of the PSD were found, large enough to contain both membrane-associated and cytoplasmic proteins of the PSD; interestingly, they were similar to nanodomains in frequency. The structures detected here appear to constitute the isolated PSD as modules of various compositions, and this modular nature may facilitate remodeling of the PSD for proper synaptic function and plasticity.
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spelling pubmed-101179892023-04-21 Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density Jung, Jae Hoon Chen, Xiaobing Reese, Thomas S. Front Synaptic Neurosci Neuroscience Postsynaptic densities (PSDs) are large protein complexes associated with the postsynaptic membrane of excitatory synapses important for synaptic function including plasticity. Conventional electron microscopy (EM) typically depicts PSDs as compact disk-like structures of hundreds of nanometers in size. Biochemically isolated PSDs were also similar in dimension revealing a predominance of proteins with the ability to polymerize into an extensive scaffold; several EM studies noted their irregular contours with often small granular structures (<30 nm) and holes. Super-resolution light microscopy studies observed clusters of PSD elements and their activity-induced lateral movement. Furthermore, our recent EM study on PSD fractions after sonication observed PSD fragments (40–90 nm in size) separate from intact PSDs; however, such structures within PSDs remained unidentified. Here we examined isolated PSDs by cryo-EM tomography with our new approach of automatic segmentation that enables delineation of substructures and their quantitative analysis. The delineated substructures broadly varied in size, falling behind 30 nm or exceeding 100 nm and showed that a considerable portion of the substructures (>38%) in isolated PSDs was in the same size range as those fragments. Furthermore, substructures spanning the entire thickness of the PSD were found, large enough to contain both membrane-associated and cytoplasmic proteins of the PSD; interestingly, they were similar to nanodomains in frequency. The structures detected here appear to constitute the isolated PSD as modules of various compositions, and this modular nature may facilitate remodeling of the PSD for proper synaptic function and plasticity. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10117989/ /pubmed/37091879 http://dx.doi.org/10.3389/fnsyn.2023.1123564 Text en Copyright © 2023 Jung, Chen and Reese. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Jung, Jae Hoon
Chen, Xiaobing
Reese, Thomas S.
Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title_full Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title_fullStr Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title_full_unstemmed Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title_short Cryo-EM tomography and automatic segmentation delineate modular structures in the postsynaptic density
title_sort cryo-em tomography and automatic segmentation delineate modular structures in the postsynaptic density
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117989/
https://www.ncbi.nlm.nih.gov/pubmed/37091879
http://dx.doi.org/10.3389/fnsyn.2023.1123564
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