Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection

Rana, Sanyukta; Yue, Shijing; Stadel, Daniela; Zöller, Margot

doi:10.1016/j.biocel.2012.06.018

Cited by 572 publications

(516 citation statements)

References 37 publications

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“…Previous observations suggest that target cell preference of exosomes is dependent on some specific combination of protein-protein interactions. Antibodyblocking studies showed that the uptake of exosomes by target cells is mediated by ligand-receptor interactions such as tetraspanin complexes and adhesion molecules (47,(53)(54)(55)(56)(57). Exosomes derived from LCLs carry an EBV glycoprotein, gp350, and then preferentially target B cells by an interaction with its ligand, CD21 (8).…”

Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells

Nanbo

Kawanishi

Yoshida

et al. 2013

J Virol

306

240

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Section: Discussionmentioning

confidence: 99%

Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells

Nanbo

Kawanishi

Yoshida

et al. 2013

J Virol

306

240

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“…For example, Hoshino et al reported that tumour cell-derived exosomes display different integrins depending on the tumour origin, and these proteins mediate tumour metastasis to specific organ sites; exosomes expressing ITGαvβ5 specifically bind to Kupffer cells and thus mediate liver tropism, whereas exosomal ITGα6β4 and ITGα6β1 bind lung-resident fibroblasts and epithelial cells to govern lung tropism [84]. Another study showed that tetraspanin-associated receptors on exosomal membranes can play an important role in target cell selection, as exosomes containing tetraspanin–integrin complexes (span8–integrin α4 complexes) could target CD54-expressing endothelial and pancreatic cells [85]. …”

Section: Therapeutic Applications Of Surface-modified Evsmentioning

confidence: 99%

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Yang

Hong

Cho

et al. 2018

J of Extracellular Vesicle

190

148

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Membrane proteins are of great research interest, particularly because they are rich in targets for therapeutic application. The suitability of various membrane proteins as targets for therapeutic formulations, such as drugs or antibodies, has been studied in preclinical and clinical studies. For therapeutic application, however, a protein must be expressed and purified in as close to its native conformation as possible. This has proven difficult for membrane proteins, as their native conformation requires the association with an appropriate cellular membrane. One solution to this problem is to use extracellular vesicles as a display platform. Exosomes and microvesicles are membranous extracellular vesicles that are released from most cells. Their membranes may provide a favourable microenvironment for membrane proteins to take on their proper conformation, activity, and membrane distribution; moreover, membrane proteins can cluster into microdomains on the surface of extracellular vesicles following their biogenesis. In this review, we survey the state-of-the-art of extracellular vesicle (exosome and small-sized microvesicle)-based therapeutics, evaluate the current biological understanding of these formulations, and forecast the technical advances that will be needed to continue driving the development of membrane protein therapeutics.

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“…According to several studies, tetraspanins CD9, CD63, CD81, CD82, CD151, Tspan8 (D6.1A), CD37, and CD53 are enriched in exosomes (78)(79)(80)(81)(82). The exact composition of the tetraspanin web on exosomes may have implications for target cell selection (83). Most TSPANs execute their function in cooperation with integrins.…”

Section: Virus Attachment Molecules Are Exposed On the Ev Surfacementioning

confidence: 99%

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

Dongen

Masoumi

Witwer

et al. 2016

Microbiol Mol Biol Rev

232

193

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SUMMARYExtracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cellsin vivoand how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors.

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Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection

Cited by 572 publications

References 37 publications

Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells

Exosomes Derived from Epstein-Barr Virus-Infected Cells Are Internalized via Caveola-Dependent Endocytosis and Promote Phenotypic Modulation in Target Cells

Extracellular vesicles as a platform for membrane‐associated therapeutic protein delivery

Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

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