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Cited by 2,832Extracellular vesicles in diseaseCellular transport and secretionNanoparticle-Based Drug Delivery

Routes and mechanisms of extracellular vesicle uptake

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Mulcahy, Laura Ann, Pink, Ryan Charles, Carter, David Raul Francisco·2014·Journal of Extracellular Vesicles
DOI 10.3402/jev.v3.24641PMC PMC4122821
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Abstract

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell‐to‐cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin‐dependent endocytosis, and clathrin‐independent pathways such as caveolin‐mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

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  • The presence of EV markers, mitochondrial, Golgi, and ER components within varicosities indicates potential roles in cellular communication, metabolic stress management, and intercellular signaling under pathological or inflammatory conditions.

    “indicating potential roles in cellular communication, metabolic stress management, and intercellular signaling under pathological or inflammatory conditions, as previously reported for reactive astrocytes (26, 42, 43).”

    From Varicose projection astrocytes: Conserved reactive cells in brain pathology (2026) · cites this paper as [26]

    The Abstract (page unavailable) describes EV-mediated intercellular exchange, signaling, and a possible role in exchanging stress-response miRNAs. It does not link EV markers or mitochondrial, Golgi, and ER components in varicosities to those functions, nor does it report metabolic stress management in reactive astrocytes under pathological or inflammatory conditions. (LLM, conf=0.86)

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References 159 · Cited by 2,832

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Authors
Mulcahy, L. A., Pink, R. C., & Carter, D. R. F.
Affiliations
Oxford Brookes University (GB)
Corresponding author
  • Mulcahy, Laura Ann
  • Carter, David Raul Francisco
ORCID
Venue
Journal of Extracellular Vesicles
Publisher
Wiley
Published
2014-01
Volume
3
Issue
1
ISSN
2001-3078 (ISSN-L)
DOI
10.3402/jev.v3.24641
PMC
PMC4122821
OpenAlex
W2003343932
Cited by
2,832
References
159
Citations by year
2026: 246 · 2025: 295 · 2024: 322 · 2023: 297 · 2022: 311 · 2021: 323 · 2020: 314 · 2019: 202 · 2018: 186 · 2017: 162 · 2016: 119 · 2015: 49 · 2014: 5 · 2013: 1
FWCI
10.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Extracellular Vesicles (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Radar (Oxford Brookes University) (submittedVersion)
Funders
  • Oxford Brookes University
  • Royal Society
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
extracellular vesicles, vesicle uptake, endocytosis, clathrin-mediated endocytosis, macropinocytosis, phagocytosis, lipid rafts, membrane fusion, cell-to-cell communication, drug delivery, cancer

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