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Cited by 804Cellular transport and secretionUbiquitin and proteasome pathwaysAutophagy in Disease and Therapy

Molecular mechanism of multivesicular body biogenesis by ESCRT complexes

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Wollert, Thomas, Hurley, James H.·2010·Nature
DOI 10.1038/nature08849PMC PMC2851844
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Abstract

When internalized receptors and other cargo are destined for lysosomal degradation, they are ubiquitinated and sorted by the endosomal sorting complex required for transport (ESCRT) complexes 0, I, II and III into multivesicular bodies. Multivesicular bodies are formed when cargo-rich patches of the limiting membrane of endosomes bud inwards by an unknown mechanism and are then cleaved to yield cargo-bearing intralumenal vesicles. The biogenesis of multivesicular bodies was reconstituted and visualized using giant unilamellar vesicles, fluorescent ESCRT-0, -I, -II and -III complexes, and a membrane-tethered fluorescent ubiquitin fusion as a model cargo. Here we show that ESCRT-0 forms domains of clustered cargo but does not deform membranes. ESCRT-I and ESCRT-II in combination deform the membrane into buds, in which cargo is confined. ESCRT-I and ESCRT-II localize to the bud necks, and recruit ESCRT-0-ubiquitin domains to the buds. ESCRT-III subunits localize to the bud neck and efficiently cleave the buds to form intralumenal vesicles. Intralumenal vesicles produced in this reaction contain the model cargo but are devoid of ESCRTs. The observations explain how the ESCRTs direct membrane budding and scission from the cytoplasmic side of the bud without being consumed in the reaction.

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  • To achieve efficient release, retroviruses hijack the host cell's ESCRT machinery, a cellular system typically involved in membrane remodeling and vesicle trafficking.

    “To achieve efficient release, retroviruses hijack the host cell’s endosomal sorting complexes required for transport (ESCRT) machinery, a cellular system typically involved in membrane remodeling and vesicle trafficking”

    From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Wollert and Hurley 2010

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Cited by

Sorted by citations

Authors
Wollert, T., & Hurley, J. H.
Affiliations
National Institutes of Health (US)
Corresponding author
Hurley, James H.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-03-21
Volume
464
Issue
7290
Pages
864-869
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature08849
PMC
PMC2851844
OpenAlex
W1987462880
Cited by
804
References
1
Citations by year
2026: 28 · 2025: 43 · 2024: 65 · 2023: 63 · 2022: 62 · 2021: 54 · 2020: 36 · 2019: 37 · 2018: 57 · 2017: 31 · 2016: 27 · 2015: 46 · 2014: 36 · 2013: 48 · 2012: 64
FWCI
30.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK036123, Z01DK036126, Z01DK036125)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
multivesicular body biogenesis, ESCRT complex, ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III, membrane budding, membrane fission, intralumenal vesicles, ubiquitination, lysosomal degradation, endosomal sorting, giant unilamellar vesicles, membrane deformation
MeSH terms
Saccharomyces cerevisiae, Cell Polarity, Protein Transport, Ubiquitin, Saccharomyces cerevisiae Proteins, Fluorescence Recovery After Photobleaching, Unilamellar Liposomes, Endosomal Sorting Complexes Required for Transport, Multivesicular Bodies

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