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.

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Author details

  1. Maria N Zanetti

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Oscar D Bello

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jing Wang

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jeff Coleman

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yiying Cai

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Charles V Sindelar

    Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. James E Rothman

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    For correspondence
    james.rothman@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8653-8650
  8. Shyam S Krishnakumar

    Department of Cell Biology, Yale School of Medicine, New Haven, United States
    For correspondence
    shyam.krishnakumar@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6148-3251

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.

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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  1. Maria N Zanetti
  2. Oscar D Bello
  3. Jing Wang
  4. Jeff Coleman
  5. Yiying Cai
  6. Charles V Sindelar
  7. James E Rothman
  8. Shyam S Krishnakumar
(2016)
Ring-like oligomers of Synaptotagmins and related c2 domain proteins
eLife 5:e17262.
https://doi.org/10.7554/eLife.17262

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https://doi.org/10.7554/eLife.17262