The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Endocytosis of Extracellular Vesicles and Release of Their Cargo from Endosomes
Open accessAbstract
Extracellular vesicles (EVs), such as exosomes, can mediate long-distance communication between cells by delivering biomolecular cargo. It is speculated that EVs undergo back-fusion at multivesicular bodies (MVBs) in recipient cells to release their functional cargo. However, direct evidence is lacking. Tracing the cellular uptake of EVs with high resolution as well as acquiring direct evidence for the release of EV cargo is challenging mainly because of technical limitations. Here, we developed an analytical methodology, combining state-of-the-art molecular tools and correlative light and electron microscopy, to identify the intracellular site for EV cargo release. GFP was loaded inside EVs through the expression of GFP-CD63, a fusion of GFP to the cytosolic tail of CD63, in EV producer cells. In addition, we genetically engineered a cell line which expresses anti-GFP fluobody that specifically recognizes the EV cargo (GFP). Incubation of anti-GFP fluobody-expressing cells with GFP-CD63 EVs resulted in the formation of fluobody punctae, designating cytosolic exposure of GFP. Endosomal damage was not observed in EV acceptor cells. Ultrastructural analysis of the underlying structures at GFP/fluobody double-positive punctae demonstrated that EV cargo release occurs from endosomes/lysosomes. Finally, we show that neutralization of endosomal pH and cholesterol accumulation in endosomes leads to blockage of EV cargo exposure. In conclusion, we report that a fraction of internalized EVs fuse with the limiting membrane of endosomes/lysosomes in an acidification-dependent manner, which results in EV cargo exposure to the cell cytosol.
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Cites
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Cited by
Welsh, J. A., Goberdhan, D. C. I., O'Driscoll, L., Buzas, E. I., Blenkiron, C., Bussolati, B., Cai, H., Di Vizio, D., Driedonks, T. A. P., Erdbrügger, U., et al. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12404 · Cited by 4,663
Challenges and directions in studying cell–cell communication by extracellular vesicles
van Niel, G., Carter, D. R. F., Clayton, A., Lambert, D. W., Raposo, G., & Vader, P. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00460-3 · Cited by 1,229
The Machinery of Exosomes: Biogenesis, Release, and Uptake
Krylova, S. V., & Feng, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021337 · Cited by 678
Recent advances in extracellular vesicles for therapeutic cargo delivery
Kim, H. I., Park, J., Zhu, Y., Wang, X., Han, Y., & Zhang, D. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01201-6 · Cited by 505
The ins-and-outs of exosome biogenesis, secretion, and internalization
Arya, S. B., Collie, S. P., & Parent, C. A. (2024) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.06.006 · Cited by 427
Metadata
- Authors
- Joshi, B. S., de Beer, M. A., Giepmans, B. N. G., & Zuhorn, I. S.
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-04-13
- Volume
- 14
- Issue
- 4
- Pages
- 4444-4455
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W3016202297
- Cited by
- 577
- References
- 79
- FWCI
- 18.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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