1. Cell Biology
  2. Genetics and Genomics

The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat

  1. Shawn P Shortill
  2. Mia S Frier
  3. Ponthakorn Wongsangaroonsri
  4. Michael Davey
  5. Elizabeth Conibear  Is a corresponding author
  1. University of British Columbia, Canada
https://doi.org/10.7554/eLife.77035
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  1. Shawn P Shortill
  2. Mia S Frier
  3. Ponthakorn Wongsangaroonsri
  4. Michael Davey
  5. Elizabeth Conibear
(2022)
The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
eLife 11:e77035.
https://doi.org/10.7554/eLife.77035
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Abstract

Membrane trafficking pathways perform important roles in establishing and maintaining the endosomal network. Retrograde protein sorting from the endosome is promoted by conserved SNX-BAR-containing coat complexes including retromer which enrich cargo at tubular microdomains and generate transport carriers. In metazoans, retromer cooperates with VARP, a conserved VPS9-domain GEF, to direct an endosomal recycling pathway. The function of the yeast VARP homolog Vrl1 has been overlooked due to an inactivating mutation found in commonly studied strains. Here, we demonstrate that Vrl1 has features of a SNX-BAR coat protein and forms an obligate complex with Vin1, the paralog of the retromer SNX-BAR protein Vps5. Unique features in the Vin1 N-terminus allow Vrl1 to distinguish it from Vps5, thereby forming a complex that we have named VINE. The VINE complex occupies endosomal tubules and redistributes a conserved mannose 6-phosphate receptor-like protein from endosomes. We also find that membrane recruitment by Vin1 is essential for Vrl1 GEF activity, suggesting that VINE is a multifunctional coat complex that regulates trafficking and signaling events at the endosome.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files; Supplemental Table 1 contains data from a genome-wide protein proximity screen and Source Data files have been provided for all graphs and blots.

Article and author information

Author details

  1. Shawn P Shortill

    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8742-7442

  2. Mia S Frier

    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5634-3235

  3. Ponthakorn Wongsangaroonsri

    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.

  4. Michael Davey

    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1172-5934

  5. Elizabeth Conibear

    Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
    For correspondence
    conibear@cmmt.ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5129-0499

Funding

Natural Sciences and Engineering Research Council of Canada (2016-04290)

  • Elizabeth Conibear

Canadian Institutes of Health Research (247169)

  • Elizabeth Conibear

Canadian Institutes of Health Research (365914)

  • Elizabeth Conibear

Canada Foundation for Innovation (Leading Edge Fund 30636)

  • Elizabeth Conibear

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

Reviewing Editor

  1. Suzanne R Pfeffer, Stanford University School of Medicine, United States

Version history

  1. Preprint posted: November 29, 2021 (view preprint)
  2. Received: January 13, 2022
  3. Accepted: August 5, 2022
  4. Accepted Manuscript published: August 8, 2022 (version 1)
  5. Version of Record published: September 23, 2022 (version 2)

Copyright

© 2022, Shortill 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. Shawn P Shortill
  2. Mia S Frier
  3. Ponthakorn Wongsangaroonsri
  4. Michael Davey
  5. Elizabeth Conibear
(2022)
The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
eLife 11:e77035.
https://doi.org/10.7554/eLife.77035

Share this article

https://doi.org/10.7554/eLife.77035

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