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Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore
SNARE-dependent membrane fusion is essential for neurotransmitter release at the synapse. Recently, α-synuclein has emerged as an important regulator for membrane fusion. Misfolded α-synuclein oligomers are potent fusion inhibitors. However, the function of normal α-synuclein has been elusive. Here,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326570/ https://www.ncbi.nlm.nih.gov/pubmed/34350173 http://dx.doi.org/10.3389/fcell.2021.663431 |
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author | Khounlo, Ryan Hawk, Brenden J. D. Khu, Tung-Mei Yoo, Gyeongji Lee, Nam Ki Pierson, Josh Shin, Yeon-Kyun |
author_facet | Khounlo, Ryan Hawk, Brenden J. D. Khu, Tung-Mei Yoo, Gyeongji Lee, Nam Ki Pierson, Josh Shin, Yeon-Kyun |
author_sort | Khounlo, Ryan |
collection | PubMed |
description | SNARE-dependent membrane fusion is essential for neurotransmitter release at the synapse. Recently, α-synuclein has emerged as an important regulator for membrane fusion. Misfolded α-synuclein oligomers are potent fusion inhibitors. However, the function of normal α-synuclein has been elusive. Here, we use the single vesicle-to-supported bilayer fusion assay to dissect the role of α-synuclein in membrane fusion. The assay employs 10 kD Rhodamine B-dextran as the content probe that can detect fusion pores larger than ∼6 nm. We find that the SNARE complex alone is inefficient at dilating fusion pores. However, α-synuclein dramatically increases the probability as well as the duration of large pores. When the SNARE-interacting C-terminal region of α-synuclein was truncated, the mutant behaves the same as the wild-type. However, the double proline mutants compromising membrane-binding show significantly reduced effects on fusion pore expansion. Thus, our results suggest that α-synuclein stimulates fusion pore expansion specifically through its membrane binding. |
format | Online Article Text |
id | pubmed-8326570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83265702021-08-03 Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore Khounlo, Ryan Hawk, Brenden J. D. Khu, Tung-Mei Yoo, Gyeongji Lee, Nam Ki Pierson, Josh Shin, Yeon-Kyun Front Cell Dev Biol Cell and Developmental Biology SNARE-dependent membrane fusion is essential for neurotransmitter release at the synapse. Recently, α-synuclein has emerged as an important regulator for membrane fusion. Misfolded α-synuclein oligomers are potent fusion inhibitors. However, the function of normal α-synuclein has been elusive. Here, we use the single vesicle-to-supported bilayer fusion assay to dissect the role of α-synuclein in membrane fusion. The assay employs 10 kD Rhodamine B-dextran as the content probe that can detect fusion pores larger than ∼6 nm. We find that the SNARE complex alone is inefficient at dilating fusion pores. However, α-synuclein dramatically increases the probability as well as the duration of large pores. When the SNARE-interacting C-terminal region of α-synuclein was truncated, the mutant behaves the same as the wild-type. However, the double proline mutants compromising membrane-binding show significantly reduced effects on fusion pore expansion. Thus, our results suggest that α-synuclein stimulates fusion pore expansion specifically through its membrane binding. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC8326570/ /pubmed/34350173 http://dx.doi.org/10.3389/fcell.2021.663431 Text en Copyright © 2021 Khounlo, Hawk, Khu, Yoo, Lee, Pierson and Shin. 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 | Cell and Developmental Biology Khounlo, Ryan Hawk, Brenden J. D. Khu, Tung-Mei Yoo, Gyeongji Lee, Nam Ki Pierson, Josh Shin, Yeon-Kyun Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title | Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title_full | Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title_fullStr | Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title_full_unstemmed | Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title_short | Membrane Binding of α-Synuclein Stimulates Expansion of SNARE-Dependent Fusion Pore |
title_sort | membrane binding of α-synuclein stimulates expansion of snare-dependent fusion pore |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326570/ https://www.ncbi.nlm.nih.gov/pubmed/34350173 http://dx.doi.org/10.3389/fcell.2021.663431 |
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