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The VINE complex is an endosomal VPS9-domain GEF and SNX-BAR coat
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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.
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Cites
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Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Retromer: A Master Conductor of Endosome Sorting
Burd, C., & Cullen, P. J. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016774 · Cited by 435
VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology
Wen, L., Tang, F.-L., Hong, Y., Luo, S.-W., Wang, C.-L., He, W., Shen, C., Jung, J.-U., Xiong, F., Lee, D.-H., et al. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201105109 · Cited by 270
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Metadata
- Authors
- Shortill, S. P., Frier, M. S., Wongsangaroonsri, P., Davey, M., & Conibear, E.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Conibear, Elizabeth
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-08-08
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9507130
- OpenAlex
- W4290648813
- Cited by
- 11
- References
- 3
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2022: 1
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Sciences and Engineering Research Council of Canada (2022-04573, PGS-D Doctoral Scholarship, CGS-M Frederick Banting and Charles Best Canada Graduate Scholarship)
- Canadian Institutes of Health Research (247169, 365914)
- Canada Foundation for Innovation (Leading Edge Fund 30636)
- BC Children's Hospital Research Institute (Jan M Friedman Graduate Studentship)
- University of British Columbia (Catalyst Paper Corporation Affiliated Fellowship, 4 Year Doctoral Fellowship, Medical Genetics Rotation Award)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- retromer, endosomal recycling, mannose 6-phosphate receptor, membrane trafficking, yeast
- MeSH terms
- Mannose, Phosphates, Endosomes, Saccharomyces cerevisiae, Guanine Nucleotide Exchange Factors, Protein Transport, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Sorting Nexins
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