Conformational Dynamics of Calcium-Triggered Activation of Fusion by Synaptotagmin

Synaptotagmin triggers rapid exocytosis of neurotransmitters from synaptic vesicles in response to Calcium (Ca2+) ions. Here, we use a novel Nanodisc-based system, designed to be a soluble mimetic of the clamped synaptic vesicle-bilayer junction, combined with fluorescence resonance energy transfer...

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Bibliographic Details
Published in:Biophysical journal 2013-12, Vol.105 (11), p.2507-2516
Main Authors: Krishnakumar, Shyam S., Kümmel, Daniel, Jones, Sunny J., Radoff, Daniel T., Reinisch, Karin M., Rothman, James E.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Calcium
Calcium - metabolism
energy transfer
exocytosis
Fluorescence
Fluorescence Resonance Energy Transfer
Ions
Lipid Bilayers - chemistry
Lipid Bilayers - metabolism
Lipids
Membrane
Mice
Molecular Dynamics Simulation
Molecular Sequence Data
Mutation
Neurotransmitters
Protein Binding
Protein Structure, Tertiary
spectroscopy
synaptic transmission
Synaptosomal-Associated Protein 25 - chemistry
Synaptosomal-Associated Protein 25 - genetics
Synaptosomal-Associated Protein 25 - metabolism
Synaptotagmin I - chemistry
Synaptotagmin I - genetics
Synaptotagmin I - metabolism
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Summary:Synaptotagmin triggers rapid exocytosis of neurotransmitters from synaptic vesicles in response to Calcium (Ca2+) ions. Here, we use a novel Nanodisc-based system, designed to be a soluble mimetic of the clamped synaptic vesicle-bilayer junction, combined with fluorescence resonance energy transfer (FRET) spectroscopy to monitor the structural relationships among SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptor), Synaptotagmin C2 domains, and the lipid bilayer in real time during the Ca2+-activation process. We report that Synaptotagmin remains rigidly fixed on the partially assembled SNARE complex with no detectable internal rearrangement of its C2 domains, even as it rapidly inserts into the bilayer. We hypothesize that this straightforward, one-step physical mechanism could explain how this Ca2+- sensor rapidly activates neurotransmitter release from the clamped state.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2013.10.029