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Ring-like Oligomers of Synaptotagmins and Related C2 Domain Proteins

Zanetti, MN; Bello, OD; Wang, J; Coleman, J; Cai, Y; Sindelar, CV; Rothman, JE; (2016) Ring-like Oligomers of Synaptotagmins and Related C2 Domain Proteins. eLIFE , 5 , Article e17262.. 10.7554/eLife.17262. Green open access

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Abstract

We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx.

Type: Article
Title: Ring-like Oligomers of Synaptotagmins and Related C2 Domain Proteins
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.17262
Publisher version: http://doi.org/10.7554/eLife.17262
Language: English
Additional information: © Copyright Zanetti et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, SPONTANEOUS NEUROTRANSMITTER RELEASE, VESICLE DOCKING, MEMBRANE-PENETRATION, SYNAPTIC VESICLE, PLASMA-MEMBRANE, CA2+ SENSOR, EXTENDED-SYNAPTOTAGMINS, TRANSMITTER RELEASE, CALCIUM-DEPENDENCE, IN-VIVO
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Clinical and Experimental Epilepsy
URI: http://discovery.ucl.ac.uk/id/eprint/1541131
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