Cited by 161Extracellular vesicles in diseaseCellular transport and secretionNanoparticle-Based Drug Delivery

Tetherin is an exosomal tether

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Edgar, James R, Manna, Paul T, Nishimura, Shinichi, Banting, George, Robinson, Margaret S·2016·eLife

Abstract

Exosomes are extracellular vesicles that are released when endosomes fuse with the plasma membrane. They have been implicated in various functions in both health and disease, including intercellular communication, antigen presentation, prion transmission, and tumour cell metastasis. Here we show that inactivating the vacuolar ATPase in HeLa cells causes a dramatic increase in the production of exosomes, which display endocytosed tracers, cholesterol, and CD63. The exosomes remain clustered on the cell surface, similar to retroviruses, which are attached to the plasma membrane by tetherin. To determine whether tetherin also attaches exosomes, we knocked it out and found a 4-fold reduction in plasma membrane-associated exosomes, with a concomitant increase in exosomes discharged into the medium. This phenotype could be rescued by wild-type tetherin but not tetherin lacking its GPI anchor. We propose that tetherin may play a key role in exosome fate, determining whether they participate in long-range or short-range interactions.

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Authors
Edgar, J. R., Manna, P. T., Nishimura, S., Banting, G., & Robinson, M. S.
Affiliations
  • University of Cambridge (GB)
  • Kyoto University (JP)
  • University of Bristol (GB)
Corresponding author
  • Edgar, James R
  • Robinson, Margaret S
Venue
eLife
Published
2016-09-22
Volume
5
ISSN
2050-084X (ISSN-L)
OpenAlex
W2521188441
Cited by
161
References
40
Citations by year
2026: 6 · 2025: 16 · 2024: 29 · 2023: 12 · 2022: 13 · 2021: 20 · 2020: 25 · 2019: 11 · 2018: 24 · 2017: 5
FWCI
7.11
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion, cc-by)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
Funders
Wellcome Trust (086598, 100140, 093026)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
tetherin, exosomes, extracellular vesicles, vacuolar ATPase, glycosylphosphatidylinositol anchor, CD63, cholesterol, intercellular communication

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