C-terminal calcium binding of α-synuclein modulates synaptic vesicle interaction
Lautenschläger J, Stephens AD, Fusco G, Ströhl F, Curry N, Zacharopoulou M, Michel CH, Laine R, Nespovitaya N, Fantham M, Pinotsi D, Zago W, Fraser P, Tandon A, St George-Hyslop P, Rees E, Phillips JJ, De Simone A, Kaminski CF, Schierle GSK (2018) Nat Commun. 2018 Feb 19;9(1): 712. doi: 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.
FAB RESEARCH COMMENT:
See the associated news story:
Food and Behaviour Research is a registered charity (No SC034604) and a company limited by guarantee (Co No SC 253448)
Newsletter Signup
Useful Links
Contact Us
FAB Research
23 Carlton Road
Oxford
OX2 7SA
Important Notice
Medical opinion and guidance should always be sought for any symptoms that might possibly reflect a known or suspected disease, disorder or medical condition. Information provided on this website (or by FAB Research via any other means) does not in any way constitute advice on the treatment of any medical condition formally diagnosed or otherwise.
Site by Redstone Websites. Easy to Use Web Content Management. 2019 © All Rights Reserved.