Details

Autor(en) / Beteiligte

• 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
• Schierle, Gabriele S Kaminski

Titel

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

Ist Teil von

• Nature communications, 2018-02, Vol.9 (1), p.712-13, Article 712

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.