COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

Abstract

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β'-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β'-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway.

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Author details

  1. Peng Xu

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hannah M Hankins

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chris MacDonald

    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Samuel J Erlinger

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8347-2617
  5. Meredith N Frazier

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Nicholas S Diab

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Robert C Piper

    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Lauren P Jackson

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3705-6126
  9. Jason A MacGurn

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5063-259X
  10. Todd R Graham

    Department of Biological Sciences, Vanderbilt University, Nashville, United States
    For correspondence
    tr.graham@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3256-2126

Funding

National Institutes of Health (5R01GM118452)

  • Todd R Graham

Pew Charitable Trusts

  • Lauren P Jackson

National Institutes of Health (5R01GM058202)

  • Robert C Piper

National Institutes of Health (1R35GM119525)

  • Lauren P Jackson

National Institutes of Health (1R01GM118491)

  • Jason A MacGurn

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Xu 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. Peng Xu
  2. Hannah M Hankins
  3. Chris MacDonald
  4. Samuel J Erlinger
  5. Meredith N Frazier
  6. Nicholas S Diab
  7. Robert C Piper
  8. Lauren P Jackson
  9. Jason A MacGurn
  10. Todd R Graham
(2017)
COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal
eLife 6:e28342.
https://doi.org/10.7554/eLife.28342

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https://doi.org/10.7554/eLife.28342

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