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

Janin Lautenschläger | Amberley D Stephens | Giuliana Fusco | Florian Ströhl | Nathan Curry | Maria Zacharopoulou | Claire H Michel | Romain Laine | Nadezhda Nespovitaya | Marcus Fantham | Dorothea Pinotsi | Wagner Zago | Paul Fraser | Anurag Tandon | Peter St George-Hyslop | Eric Rees | Jonathan J Phillips | Alfonso De Simone | Clemens F Kaminski | Gabriele S Kaminski Schierle
Nature communications | 2018

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.

Pubmed ID: 29459792

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/K02292X/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/N000676/1
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Medical Research Council, United Kingdom
    Id: G0902243
  • Agency: Biotechnology and Biological Sciences Research Council, United Kingdom
    Id: BB/H023917/1
  • Agency: Wellcome Trust, United Kingdom
    Id: 203249/Z/16/Z
  • Agency: Parkinson's UK, United Kingdom
    Id: G-1508

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