C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction.
View / Open Files
Authors
Lautenschläger, Janin
Fusco, Giuliana
Curry, Nathan
Zacharopoulou, Maria
Michel, Claire H
Laine, Romain
Nespovitaya, Nadezhda
Fantham, Marcus
Pinotsi, Dorothea
Zago, Wagner
Fraser, Paul
Tandon, Anurag
Rees, Eric
De Simone, Alfonso
Publication Date
2018-02-19Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
9
Issue
1
Pages
712
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Lautenschläger, J., Stephens, A. D., Fusco, G., Ströhl, F., Curry, N., Zacharopoulou, M., Michel, C. H., et al. (2018). C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction.. Nat Commun, 9 (1), 712. https://doi.org/10.1038/s41467-018-03111-4
Abstract
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.
Keywords
Presynaptic Terminals, Synaptic Vesicles, Cell Line, Synaptosomes, Animals, Humans, Rats, Rats, Sprague-Dawley, Calcium, Microscopy, Electron, Transmission, Nuclear Magnetic Resonance, Biomolecular, Binding Sites, Protein Binding, Lipid Metabolism, alpha-Synuclein, In Vitro Techniques, Protein Aggregates
Sponsorship
Medical Research Council (MR/K02292X/1)
Alzheimer's Research UK (ARUK-PG2013-14)
Biotechnology and Biological Sciences Research Council (BB/H023917/1)
Engineering and Physical Sciences Research Council (EP/H018301/1)
Medical Research Council (G0902243)
Wellcome Trust (203249/Z/16/Z)
Identifiers
External DOI: https://doi.org/10.1038/s41467-018-03111-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/278584
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The following licence files are associated with this item: