دورية أكاديمية
C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction
العنوان: | C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction |
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المؤلفون: | Lautenschläger, Janin, Stephens, Amberley D., Fusco, Giuliana, Ströhl, Florian, Curry, Nathan, Zacharopoulou, Maria, Michel, Claire H., Laine, Romain, Nespovitaya, Nadezhda, Fantham, Marcus, Pinotsi, Dorothea, Zago, Wagner, Fraser, Paul, Tandon, Anurag, St George-Hyslop, Peter, Rees, Eric, Phillips, Jonathan J., De Simone, Alfonso, Kaminski, Clemens F., Kaminski Schierle, Gabriele S. |
المصدر: | Nature Communications, 9 |
بيانات النشر: | Nature |
سنة النشر: | 2018 |
المجموعة: | ETH Zürich Research Collection |
الوصف: | Alpha-synuclein is known to bind to small unilamellar vesicles (SUVs) via its N terminus, which forms an amphipathic alpha-helix upon membrane interaction. Here we show that calcium binds to the C terminus of alpha-synuclein, therewith increasing its lipid-binding capacity. Using CEST-NMR, we reveal that alpha-synuclein interacts with isolated synaptic vesicles with two regions, the N terminus, already known from studies on SUVs, and additionally via its C terminus, which is regulated by the binding of calcium. Indeed, dSTORM on synaptosomes shows that calcium mediates the localization of alpha-synuclein at the pre-synaptic terminal, and an imbalance in calcium or alpha-synuclein can cause synaptic vesicle clustering, as seen ex vivo and in vitro. This study provides a new view on the binding of alpha-synuclein to synaptic vesicles, which might also affect our understanding of synucleinopathies. ; ISSN:2041-1723 |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/application/pdf |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/wos/000425382800004; http://hdl.handle.net/20.500.11850/244531Test |
DOI: | 10.3929/ethz-b-000244531 |
الإتاحة: | https://doi.org/20.500.11850/244531Test https://doi.org/10.3929/ethz-b-000244531Test https://doi.org/10.1038/s41467-018-03111-4Test https://hdl.handle.net/20.500.11850/244531Test |
حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0Test/ ; Creative Commons Attribution 4.0 International |
رقم الانضمام: | edsbas.F6E0E652 |
قاعدة البيانات: | BASE |
DOI: | 10.3929/ethz-b-000244531 |
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