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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...

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Autores principales: Martinez-Sanchez, Antonio, Laugks, Ulrike, Kochovski, Zdravko, Papantoniou, Christos, Zinzula, Luca, Baumeister, Wolfgang, Lučić, Vladan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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.
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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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