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

Author

Listed:
  • Janin Lautenschläger

    (University of Cambridge)

  • Amberley D. Stephens

    (University of Cambridge)

  • Giuliana Fusco

    (University of Cambridge
    Imperial College London)

  • Florian Ströhl

    (University of Cambridge)

  • Nathan Curry

    (University of Cambridge)

  • Maria Zacharopoulou

    (University of Cambridge)

  • Claire H. Michel

    (University of Cambridge)

  • Romain Laine

    (University of Cambridge)

  • Nadezhda Nespovitaya

    (University of Cambridge)

  • Marcus Fantham

    (University of Cambridge)

  • Dorothea Pinotsi

    (University of Cambridge
    Scientific Center for Optical and Electron Microscopy)

  • Wagner Zago

    (Prothena Biosciences Inc)

  • Paul Fraser

    (University of Toronto)

  • Anurag Tandon

    (University of Toronto)

  • Peter St George-Hyslop

    (University of Toronto
    University of Cambridge)

  • Eric Rees

    (University of Cambridge)

  • Jonathan J. Phillips

    (University of Exeter)

  • Alfonso De Simone

    (Imperial College London)

  • Clemens F. Kaminski

    (University of Cambridge)

  • Gabriele S. Kaminski Schierle

    (University of Cambridge)

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.

Suggested Citation

  • Janin Lautenschläger & Amberley D. Stephens & Giuliana Fusco & Florian Ströhl & Nathan Curry & Maria Zacharopoulou & Claire H. Michel & Romain Laine & Nadezhda Nespovitaya & Marcus Fantham & Dorothea , 2018. "C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03111-4
    DOI: 10.1038/s41467-018-03111-4
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