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A role for Vps13-mediated lipid transfer at the ER-endosome contact site in ESCRT-mediated sorting
Open accessPreprint — published as 10.1083/jcb.202307094
Abstract
Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intralumenal vesicles (ILVs) at endosomes by E ndosomal S orting C omplex R equired for T ransport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite consumption of the limiting membrane during ILV formation. Vesicle-mediated trafficking is thought to provide lipids to support MVB biogenesis. However, we have uncovered an unexpected contribution of a large bridge-like lipid transfer protein, Vps13, in this process. Here, we reveal that Vps13-mediated lipid transfer at ER-endosome contact sites is required for the ESCRT pathway. We propose that Vps13 may play a critical role in supplying lipids to the endosome, ensuring continuous ESCRT-mediated sorting during MVB formation.
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Highly accurate protein structure prediction with AlphaFold
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
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Metadata
- Authors
- Suzuki, S. W., West, M., Zhang, Y., Fan, J. S., Roberts, R. T., Odorizzi, G., & Emr, S. D.
- Affiliations
- Nanyang Technological University (SG)
- University of Colorado Boulder (US)
- Cornell University (US)
- Corresponding author
- Suzuki, Sho W.
- ORCID
- Venue
- The Journal of Cell Biology
- Publisher
- openRxiv
- Published
- 2023-07-07
- Volume
- 223
- Issue
- 4
- ISSN
- 0021-9525 (ISSN-L)
- PMC
- PMC10847051
- OpenAlex
- W4391564828
- Cited by
- 24
- References
- 1
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 2
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (publishedVersion, cc-by-nc-sa)
- Funders
- Cornell University (CU563704)
- University of Tokyo
- National Institute of General Medical Sciences (R35GM149202)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- Vps13, lipid transfer, ESCRT, multivesicular bodies, endosomal sorting, endosomal maturation, lysosomal degradation
- MeSH terms
- Endocytosis, Lipids, Endosomes, Saccharomyces cerevisiae, Protein Transport, Saccharomyces cerevisiae Proteins, Endosomal Sorting Complexes Required for Transport, Multivesicular Bodies
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