1. Cell Biology
  2. Neuroscience

Synaptotagmin 1 directs repetitive release by coupling vesicle exocytosis to the Rab3 cycle

  1. Yunsheng Cheng
  2. Jiaming Wang
  3. Yu Wang
  4. Mei Ding  Is a corresponding author
  1. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, China
https://doi.org/10.7554/eLife.05118
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  1. Yunsheng Cheng
  2. Jiaming Wang
  3. Yu Wang
  4. Mei Ding
(2015)
Synaptotagmin 1 directs repetitive release by coupling vesicle exocytosis to the Rab3 cycle
eLife 4:e05118.
https://doi.org/10.7554/eLife.05118
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Abstract

In response to Ca2+ influx, a synapse needs to release neurotransmitters quickly while immediately preparing for repeat firing. How this harmonization is achieved is not known. Here, we found that the Ca2+ sensor synaptotagmin 1 orchestrates the membrane association/disassociation cycle of Rab3, which functions in activity-dependent recruitment of synaptic vesicles. In the absence of Ca2+, synaptotagmin 1 binds to Rab3 GTPase activating protein (GAP) and inhibits the GTP hydrolysis of Rab3 protein. Rab3 GAP resides on synaptic vesicles and synaptotagmin 1 is essential for the synaptic localization of Rab3 GAP. In the presence of Ca2+, synaptotagmin 1 releases Rab3 GAP and promotes membrane disassociation of Rab3. Without synaptotagmin 1, the tight coupling between vesicle exocytosis and Rab3 membrane disassociation is disrupted. We uncovered the long-sought molecular apparatus linking vesicle exocytosis to Rab3 cycling and we also revealed the important function of synaptotagmin 1 in repetitive synaptic vesicle release.

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Author details

  1. Yunsheng Cheng

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Jiaming Wang

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Yu Wang

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Mei Ding

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    For correspondence
    mding@genetics.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Reinhard Jahn, Max Planck Institute for Biophysical Chemistry, Germany

Version history

  1. Received: October 10, 2014
  2. Accepted: February 23, 2015
  3. Accepted Manuscript published: February 24, 2015 (version 1)
  4. Version of Record published: March 26, 2015 (version 2)

Copyright

© 2015, Cheng 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. Yunsheng Cheng
  2. Jiaming Wang
  3. Yu Wang
  4. Mei Ding
(2015)
Synaptotagmin 1 directs repetitive release by coupling vesicle exocytosis to the Rab3 cycle
eLife 4:e05118.
https://doi.org/10.7554/eLife.05118

Share this article

https://doi.org/10.7554/eLife.05118

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