1. Physics of Living Systems

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis

  1. Lu Ma
  2. Aleksander A Rebane
  3. Guangcan Yang
  4. Zhiqun Xi
  5. Yuhao Kang
  6. Ying Gao
  7. Yongli Zhang  Is a corresponding author
  1. Yale University School of Medicine, United States
  2. Yale School of Medicine, United States
  3. Yale University, School of Medicine, United States
https://doi.org/10.7554/eLife.09580
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  1. Lu Ma
  2. Aleksander A Rebane
  3. Guangcan Yang
  4. Zhiqun Xi
  5. Yuhao Kang
  6. Ying Gao
  7. Yongli Zhang
(2015)
Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis
eLife 4:e09580.
https://doi.org/10.7554/eLife.09580
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Abstract

Synaptic soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

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Author details

  1. Lu Ma

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

  2. Aleksander A Rebane

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

  3. Guangcan Yang

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

  4. Zhiqun Xi

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

  5. Yuhao Kang

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

  6. Ying Gao

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

  7. Yongli Zhang

    Department of Cell Biology, Yale University, School of Medicine, New Haven, United States
    For correspondence
    yongli.zhang@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Stephen C. Harrison, Harvard Medical School, United States

Version history

  1. Received: June 23, 2015
  2. Accepted: December 22, 2015
  3. Accepted Manuscript published: December 23, 2015 (version 1)
  4. Version of Record published: January 27, 2016 (version 2)
  5. Version of Record updated: March 21, 2016 (version 3)

Copyright

© 2015, Ma 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. Lu Ma
  2. Aleksander A Rebane
  3. Guangcan Yang
  4. Zhiqun Xi
  5. Yuhao Kang
  6. Ying Gao
  7. Yongli Zhang
(2015)
Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis
eLife 4:e09580.
https://doi.org/10.7554/eLife.09580

Share this article

https://doi.org/10.7554/eLife.09580

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