Ramakrishnan, S;
Bera, M;
Coleman, J;
Krishnakumar, SS;
Pincet, F;
Rothman, JE;
(2019)
Synaptotagmin oligomers are necessary and can be sufficient to form a Ca2+-sensitive fusion clamp.
FEBS Letters
, 593
(2)
pp. 154-162.
10.1002/1873-3468.13317.
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Abstract
The buttressed-ring hypothesis, supported by recent cryo-electron tomography analysis of docked synaptic-like vesicles in neuroendocrine cells, postulates that prefusion SNAREpins are stabilized and organized by Synaptotagmin (Syt) ring-like oligomers. Here, we use a reconstituted single-vesicle fusion analysis to test the prediction that destabilizing the Syt1 oligomers destabilizes the clamp and results in spontaneous fusion in the absence of Ca2+. Vesicles in which Syt oligomerization is compromised by a ring-destabilizing mutation dock and diffuse freely on the bilayer until they fuse spontaneously, similar to vesicles containing only v-SNAREs. In contrast, vesicles containing wild-type Syt are immobile as soon as they attach to the bilayer and remain frozen in place, up to at least 1 h until fusion is triggered by Ca2+.
| Type: | Article |
|---|---|
| Title: | Synaptotagmin oligomers are necessary and can be sufficient to form a Ca2+-sensitive fusion clamp |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/1873-3468.13317 |
| Publisher version: | http://doi.org/10.1002/1873-3468.13317 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | calcium; fusion clamp; single-vesicle analysis; SNARE proteins; Synaptotagmin |
| 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/10075270 |
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