Li, X;
Radhakrishnan, A;
Grushin, K;
Kasula, R;
Chaudhuri, A;
Gomathinayagam, S;
Krishnakumar, SS;
... Rothman, JE; + view all
(2019)
Symmetrical organization of proteins under docked synaptic vesicles.
FEBS Letters
, 593
(2)
pp. 144-153.
10.1002/1873-3468.13316.
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Abstract
During calcium‐regulated exocytosis, the constitutive fusion machinery is ‘clamped’ in a partially assembled state until synchronously released by calcium. The protein machinery involved in this process is known, but the supra‐molecular architecture and underlying mechanisms are unclear. Here, we use cryo‐electron tomography analysis in nerve growth factor‐differentiated neuro‐endocrine (PC12) cells to delineate the organization of the release machinery under the docked vesicles. We find that exactly six exocytosis modules, each likely consisting of a single SNAREpin with its bound Synaptotagmins, Complexin, and Munc18 proteins, are symmetrically arranged at the vesicle–PM interface. Mutational analysis suggests that the symmetrical organization is templated by circular oligomers of Synaptotagmin. The observed arrangement, including its precise radial positioning, is in‐line with the recently proposed ‘buttressed ring hypothesis’.
| Type: | Article |
|---|---|
| Title: | Symmetrical organization of proteins under docked synaptic vesicles |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/1873-3468.13316 |
| Publisher version: | https://doi.org/10.1002/1873-3468.13316 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biophysics, Cell Biology, cryo-electron tomography, PC12 cells, regulated exocytosis, SNARE proteins, synaptotagmin, SNARE COMPLEX, FUSION, RECONSTRUCTION, VISUALIZATION, SUFFICIENT, RELEASE, SYSTEM, CELLS |
| 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-pp.ucl.ac.uk/id/eprint/10075607 |
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