Ring-like oligomers of Synaptotagmins and related c2 domain proteins
- Yale School of Medicine, United States
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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.
Article and author information
Author details
Shyam S Krishnakumar
Funding
National Institute of General Medical Sciences (GM071458)
- James E Rothman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Axel T Brunger, Howard Hughes Medical Institute, Stanford University, United States
Publication history
- Received: April 26, 2016
- Accepted: July 18, 2016
- Accepted Manuscript published: July 19, 2016 (version 1)
- Version of Record published: August 8, 2016 (version 2)
Copyright
© 2016, Zanetti et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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