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C-terminal calcium binding of alpha-synuclein modulates synaptic vesicle interaction

Lautenschlager, J; Stephens, AD; Fusco, G; Strohl, F; Curry, N; Zacharopoulou, M; Michel, CH; ... Schierle, GSK; + view all (2018) C-terminal calcium binding of alpha-synuclein modulates synaptic vesicle interaction. Nature Communications , 9 , Article 712. 10.1038/s41467-018-03111-4. Green open access

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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.

Type: Article
Title: C-terminal calcium binding of alpha-synuclein modulates synaptic vesicle interaction
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-018-03111-4
Publisher version: https://doi.org/10.1038/s41467-018-03111-4
Language: English
Additional information: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Molecular neuroscience, Neuroscience
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10079991
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