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Trans-synaptic assemblies link synaptic vesicles and neuroreceptors
Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo–electron tomography to visualize synap...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935360/ https://www.ncbi.nlm.nih.gov/pubmed/33674312 http://dx.doi.org/10.1126/sciadv.abe6204 |
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author | Martinez-Sanchez, Antonio Laugks, Ulrike Kochovski, Zdravko Papantoniou, Christos Zinzula, Luca Baumeister, Wolfgang Lučić, Vladan |
author_facet | Martinez-Sanchez, Antonio Laugks, Ulrike Kochovski, Zdravko Papantoniou, Christos Zinzula, Luca Baumeister, Wolfgang Lučić, Vladan |
author_sort | Martinez-Sanchez, Antonio |
collection | PubMed |
description | Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo–electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2- to 4-nm scale. Using template-free detection and classification, we showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. These data support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function. |
format | Online Article Text |
id | pubmed-7935360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79353602021-03-17 Trans-synaptic assemblies link synaptic vesicles and neuroreceptors Martinez-Sanchez, Antonio Laugks, Ulrike Kochovski, Zdravko Papantoniou, Christos Zinzula, Luca Baumeister, Wolfgang Lučić, Vladan Sci Adv Research Articles Synaptic transmission is characterized by fast, tightly coupled processes and complex signaling pathways that require a precise protein organization, such as the previously reported nanodomain colocalization of pre- and postsynaptic proteins. Here, we used cryo–electron tomography to visualize synaptic complexes together with their native environment comprising interacting proteins and lipids on a 2- to 4-nm scale. Using template-free detection and classification, we showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic receptors and established that a particular displacement between directly interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. These data support the hypothesis that synaptic function is carried by precisely organized trans-synaptic units. It provides a framework for further exploration of synaptic and other large molecular assemblies that link different cells or cellular regions and may require weak or transient interactions to exert their function. American Association for the Advancement of Science 2021-03-05 /pmc/articles/PMC7935360/ /pubmed/33674312 http://dx.doi.org/10.1126/sciadv.abe6204 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Martinez-Sanchez, Antonio Laugks, Ulrike Kochovski, Zdravko Papantoniou, Christos Zinzula, Luca Baumeister, Wolfgang Lučić, Vladan Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title | Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title_full | Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title_fullStr | Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title_full_unstemmed | Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title_short | Trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
title_sort | trans-synaptic assemblies link synaptic vesicles and neuroreceptors |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935360/ https://www.ncbi.nlm.nih.gov/pubmed/33674312 http://dx.doi.org/10.1126/sciadv.abe6204 |
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