The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
- University of British Columbia, Canada
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
Elizabeth Conibear
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.
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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The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
eLife 11:e77035.
https://doi.org/10.7554/eLife.77035
