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Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein
Although numerous studies have shown that the protein α-synuclein (α-Syn) plays a central role in Parkinson’s disease, dementia with Lewy bodies, and other neurodegenerative diseases, the protein’s physiological function remains poorly understood. Furthermore, despite recent reports suggesting that,...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433175/ https://www.ncbi.nlm.nih.gov/pubmed/34567651 http://dx.doi.org/10.1038/s41378-020-0147-1 |
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author | Cai, Bin Liu, Jie Zhao, Yunfei Xu, Xiangyu Bu, Bing Li, Dechang Zhang, Lei Dong, Wei Ji, Baohua Diao, Jiajie |
author_facet | Cai, Bin Liu, Jie Zhao, Yunfei Xu, Xiangyu Bu, Bing Li, Dechang Zhang, Lei Dong, Wei Ji, Baohua Diao, Jiajie |
author_sort | Cai, Bin |
collection | PubMed |
description | Although numerous studies have shown that the protein α-synuclein (α-Syn) plays a central role in Parkinson’s disease, dementia with Lewy bodies, and other neurodegenerative diseases, the protein’s physiological function remains poorly understood. Furthermore, despite recent reports suggesting that, under the influence of Ca(2+), α-Syn can interact with synaptic vesicles, the mechanisms underlying that interaction are far from clear. Thus, we used single-vesicle imaging to quantify the extent to which Ca(2+) regulates nanoscale vesicle clustering mediated by α-Syn. Our results revealed not only that vesicle clustering required α-Syn to bind to anionic lipid vesicles, but also that different concentrations of Ca(2+) exerted different effects on how α-Syn induced vesicle clustering. In particular, low concentrations of Ca(2+) inhibited vesicle clustering by blocking the electrostatic interaction between the lipid membrane and the N terminus of α-Syn, whereas high concentrations promoted vesicle clustering, possibly due to the electrostatic interaction between Ca(2+) and the negatively charged lipids that is independent of α-Syn. Taken together, our results provide critical insights into α-Syn’s physiological function, and how Ca(2+) regulates vesicle clustering mediated by α-Syn. |
format | Online Article Text |
id | pubmed-8433175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84331752021-09-24 Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein Cai, Bin Liu, Jie Zhao, Yunfei Xu, Xiangyu Bu, Bing Li, Dechang Zhang, Lei Dong, Wei Ji, Baohua Diao, Jiajie Microsyst Nanoeng Article Although numerous studies have shown that the protein α-synuclein (α-Syn) plays a central role in Parkinson’s disease, dementia with Lewy bodies, and other neurodegenerative diseases, the protein’s physiological function remains poorly understood. Furthermore, despite recent reports suggesting that, under the influence of Ca(2+), α-Syn can interact with synaptic vesicles, the mechanisms underlying that interaction are far from clear. Thus, we used single-vesicle imaging to quantify the extent to which Ca(2+) regulates nanoscale vesicle clustering mediated by α-Syn. Our results revealed not only that vesicle clustering required α-Syn to bind to anionic lipid vesicles, but also that different concentrations of Ca(2+) exerted different effects on how α-Syn induced vesicle clustering. In particular, low concentrations of Ca(2+) inhibited vesicle clustering by blocking the electrostatic interaction between the lipid membrane and the N terminus of α-Syn, whereas high concentrations promoted vesicle clustering, possibly due to the electrostatic interaction between Ca(2+) and the negatively charged lipids that is independent of α-Syn. Taken together, our results provide critical insights into α-Syn’s physiological function, and how Ca(2+) regulates vesicle clustering mediated by α-Syn. Nature Publishing Group UK 2020-06-29 /pmc/articles/PMC8433175/ /pubmed/34567651 http://dx.doi.org/10.1038/s41378-020-0147-1 Text en © The Author(s) 2020 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 Cai, Bin Liu, Jie Zhao, Yunfei Xu, Xiangyu Bu, Bing Li, Dechang Zhang, Lei Dong, Wei Ji, Baohua Diao, Jiajie Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title | Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title_full | Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title_fullStr | Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title_full_unstemmed | Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title_short | Single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
title_sort | single-vesicle imaging quantifies calcium’s regulation of nanoscale vesicle clustering mediated by α-synuclein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433175/ https://www.ncbi.nlm.nih.gov/pubmed/34567651 http://dx.doi.org/10.1038/s41378-020-0147-1 |
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