Wang, J;
Li, F;
Bello, OD;
Sindelar, CV;
Pincet, F;
Krishnakumar, SS;
Rothman, JE;
(2017)
Circular oligomerization is an intrinsic property of synaptotagmin.
eLife
, 6
, Article e27441. 10.7554/eLife.27441.
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Abstract
Previously, we showed that synaptotagmin1 (Syt1) forms Ca(2+)-sensitive ring-like oligomers on membranes containing acidic lipids and proposed a potential role in regulating neurotransmitter release (Zanetti et al., 2016). Here, we report that Syt1 assembles into similar ring-like oligomers in solution when triggered by naturally occurring polyphosphates (PIP2 and ATP) and magnesium ions (Mg(2+)). These soluble Syt1 rings were observed by electron microscopy and independently demonstrated and quantified using fluorescence correlation spectroscopy. Oligomerization is triggered when polyphosphates bind to the polylysine patch in C2B domain and is stabilized by Mg(2+), which neutralizes the Ca(2+)-binding aspartic acids that likely contribute to the C2B interface in the oligomer. Overall, our data show that ring-like polymerization is an intrinsic property of Syt1 with reasonable affinity that can be triggered by the vesicle docking C2B-PIP2 interaction and raise the possibility that Syt1 rings could pre-form on the synaptic vesicle to facilitate docking.
Type: | Article |
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Title: | Circular oligomerization is an intrinsic property of synaptotagmin |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.7554/eLife.27441 |
Publisher version: | https://doi.org/10.7554/eLife.27441 |
Language: | English |
Additional information: | Copyright © Wang et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | E. coli, electron microscopy, membrane fusion, neuroscience, neurotransmitters |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
URI: | https://discovery.ucl.ac.uk/id/eprint/1572547 |
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