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Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane

Synaptic vesicles are small membrane-enclosed organelles that store neurotransmitters at presynaptic terminals. The uniform morphology of synaptic vesicles is important for brain function, because it enables the storage of well-defined amounts of neurotransmitters and thus reliable synaptic transmis...

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Autores principales: Yu, Taekyung, Flores-Solis, David, Eastep, Gunnar N., Becker, Stefan, Zweckstetter, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352133/
https://www.ncbi.nlm.nih.gov/pubmed/37217654
http://dx.doi.org/10.1038/s41594-023-01004-9
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author Yu, Taekyung
Flores-Solis, David
Eastep, Gunnar N.
Becker, Stefan
Zweckstetter, Markus
author_facet Yu, Taekyung
Flores-Solis, David
Eastep, Gunnar N.
Becker, Stefan
Zweckstetter, Markus
author_sort Yu, Taekyung
collection PubMed
description Synaptic vesicles are small membrane-enclosed organelles that store neurotransmitters at presynaptic terminals. The uniform morphology of synaptic vesicles is important for brain function, because it enables the storage of well-defined amounts of neurotransmitters and thus reliable synaptic transmission. Here, we show that the synaptic vesicle membrane protein synaptogyrin cooperates with the lipid phosphatidylserine to remodel the synaptic vesicle membrane. Using NMR spectroscopy, we determine the high-resolution structure of synaptogyrin and identify specific binding sites for phosphatidylserine. We further show that phosphatidylserine binding changes the transmembrane structure of synaptogyrin and is critical for membrane bending and the formation of small vesicles. Cooperative binding of phosphatidylserine to both a cytoplasmic and intravesicular lysine-arginine cluster in synaptogyrin is required for the formation of small vesicles. Together with other synaptic vesicle proteins, synaptogyrin thus can sculpt the membrane of synaptic vesicles.
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spelling pubmed-103521332023-07-19 Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane Yu, Taekyung Flores-Solis, David Eastep, Gunnar N. Becker, Stefan Zweckstetter, Markus Nat Struct Mol Biol Article Synaptic vesicles are small membrane-enclosed organelles that store neurotransmitters at presynaptic terminals. The uniform morphology of synaptic vesicles is important for brain function, because it enables the storage of well-defined amounts of neurotransmitters and thus reliable synaptic transmission. Here, we show that the synaptic vesicle membrane protein synaptogyrin cooperates with the lipid phosphatidylserine to remodel the synaptic vesicle membrane. Using NMR spectroscopy, we determine the high-resolution structure of synaptogyrin and identify specific binding sites for phosphatidylserine. We further show that phosphatidylserine binding changes the transmembrane structure of synaptogyrin and is critical for membrane bending and the formation of small vesicles. Cooperative binding of phosphatidylserine to both a cytoplasmic and intravesicular lysine-arginine cluster in synaptogyrin is required for the formation of small vesicles. Together with other synaptic vesicle proteins, synaptogyrin thus can sculpt the membrane of synaptic vesicles. Nature Publishing Group US 2023-05-22 2023 /pmc/articles/PMC10352133/ /pubmed/37217654 http://dx.doi.org/10.1038/s41594-023-01004-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yu, Taekyung
Flores-Solis, David
Eastep, Gunnar N.
Becker, Stefan
Zweckstetter, Markus
Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title_full Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title_fullStr Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title_full_unstemmed Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title_short Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
title_sort phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352133/
https://www.ncbi.nlm.nih.gov/pubmed/37217654
http://dx.doi.org/10.1038/s41594-023-01004-9
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