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Cited by 46Cellular transport and secretionAutophagy in Disease and TherapyUbiquitin and proteasome pathways

Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos

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Frankel, E. B., Shankar, Raakhee, Moresco, James J., Yates, John R., Volkmann, Niels, Audhya, Anjon·2017·Nature Communications
DOI 10.1038/s41467-017-01636-8PMC PMC5682282
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Abstract

Degradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans. In contrast to previous models suggesting that ILVs form individually, we demonstrate that they remain tethered to one another subsequent to internalization, arguing that they bud continuously from stable subdomains. In addition, we show that membrane bending and ILV formation are directed specifically by the ESCRT-III complex in vivo in a manner regulated by Ist1, which promotes ESCRT-III assembly and inhibits the incorporation of upstream ESCRT components into ILVs. Our findings underscore essential actions for ESCRT-III in membrane remodeling, cargo selection, and cargo retention, which act repetitively to maximize the rate of ILV formation.

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  • Newly formed ILVs from the limiting membrane of some MVBs are physically attached via electron dense tethers with an approximate width of ~12 nm.

    “it has recently been observed that newly formed intraluminal vesicles (ILVs) from the limiting membrane of some multi-vesicular bodies (MVBs), the compartments that produce exosomes, are physically attached to each other via electron dense tethers with an approximate width of ~12 nm36.”

    From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [36]

    The Results section, “ILVs remain physically connected following internalization” (page not provided), reports newly formed ILVs clustered near the limiting membrane and connected to one another by electron-dense tethers. The cited ~12 nm measurement is tether length (12 ± 5 nm), not width; the reported width is 18 ± 7 nm in zygotes. (LLM, conf=0.93)

    Experimental — accuracy not yet measured

  • Clustered ILVs have been observed in other cell types in mammals and nematodes in the absence of DCGs and in specific pathological scenarios.

    “Indeed, clustered ILVs have been observed in other cell types in mammals and nematodes in the absence of DCGs and in specific pathological scenarios36,64.”

    From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [36]

    The Results section, “ILVs remain physically connected following internalization” (page unavailable), reports contacting, tethered ILVs in C. elegans hypodermal cells, supporting the nematode-cell observation. Our copy does not establish that DCGs were absent in those cells, and it does not report the claimed mammalian or pathological observations. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The MVBs involved in these studies may not be classical late-endosomes.

    “One common feature in these studies is that the MVBs involved may not be classical late-endosomes.”

    From GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain (2021) · cites this paper as [36]

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Authors
Frankel, E. B., Shankar, R., Moresco, J. J., Yates, J. R., Volkmann, N., & Audhya, A.
Affiliations
  • University of Wisconsin–Madison (US)
  • Scripps Research Institute (US)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
Audhya, Anjon
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-11-13
Volume
8
Issue
1
Pages
1439-1439
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-01636-8
PMC
PMC5682282
OpenAlex
W2767670983
Cited by
46
References
2
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 5 · 2020: 5 · 2019: 6 · 2018: 2
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Wisconsin Alumni Research Foundation
  • University of Wisconsin-Madison
  • National Institutes of Health (GM088151, GM103533)
  • National Institute of General Medical Sciences (R01GM115972, P41GM103533, R01GM088151, T32GM007215, R01GM110567)
  • Division of Graduate Education
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
IST1, ESCRT-III, membrane bending, membrane remodeling, oocyte-to-embryo transition, Caenorhabditis elegans embryo, membrane internalization
MeSH terms
Animals, Cell Membrane, Oocytes, Caenorhabditis elegans, Protein Transport, Caenorhabditis elegans Proteins, Vesicular Transport Proteins, RNA Interference, RNA, Small Interfering, Adaptor Proteins, Signal Transducing, Endosomal Sorting Complexes Required for Transport, Multivesicular Bodies

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