Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes

By Katarina Trajković, Chieh Hsu, S. Chiantia, L. Rajendran, Dirk Wenzel, F. Wieland, P. Schwille, B. Brügger, M. Simons. Science, 2008

3,426 citations recorded by the source corpus.

Intraluminal vesicles of multivesicular endosomes are either sorted for cargo degradation into lysosomes or secreted as exosomes into the extracellular milieu. The mechanisms underlying the sorting of membrane into the different populations of intraluminal vesicles are unknown. Here, we find that cargo is segregated into distinct subdomains on the endosomal membrane and that the transfer of exosome-associated domains into the lumen of the endosome did not depend on the function of the ESCRT (endosomal sorting complex required for transport) machinery, but required the sphingolipid ceramide. Purified exosomes were enriched in ceramide, and the release of exosomes was reduced after the inhibition of neutral sphingomyelinases. These results establish a pathway in intraendosomal membrane transport and exosome formation.

View Paper: https://www.semanticscholar.org/paper/1c02595b574acf9919f0d704d94b0c9197b4a39f

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Citations in the corpus

Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C (2010, methodology): “Exosome purification Exosomes were prepared as described previously (Trajkovic et al., 2008).”
Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. (2012, methodology): “was later investigated by the Simons lab [12], which showed that the sphingolipid ceramide plays a key role in the genesis of exosomal,”
Exosomes as Critical Agents of Cardiac Regeneration Triggered by Cell Therapy (2014, methodology): “To test this concept, we treated CDCs with GW4869, a reversible inhibitor of neutral sphingomyelinase that prevents exosome release (Kosaka et al., 2010; Trajkovic et al., 2008).”
Extracellular vesicles: Exosomes, microvesicles, and friends (2013, background): “These observations are consistent with the presence of high concentrations of ceramide and derivatives thereof in exosomes (Wubbolts et al., 2003; Trajkovic et al., 2008; Brouwers et al., 2012).”
Biodistribution and Delivery Efficiency of Unmodified Tumor-Derived Exosomes (2014, methodology): “Liposomes in this work were prepared to either mimic the lipid composition of exosomes (SynExoLiposomes) [24,28–32], or to be comparable to a widely studied liposomal formulation, PC:Chol.”
Interaction and uptake of exosomes by ovarian cancer cells (2011, background): “However, some proteins present in the exosomes are not ubiquitinated suggesting that other mechanisms such as oligomerization or partitioning of protein into lipid raft domains may be involved [6-9].”
Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes (2019, background): “Ceramide is synthesized from sphingomyelin by sphingomyelinase 2 (nSMase2) and the inhibition of this enzyme reduces the exosomal release of the proteolipid protein in Oli-neu cells [48].”
Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles (2013, background): “This fully corroborates the observations that cells contain different MVBs and that within MVBs, ILVs are not all similar in morphology and composition (Fevrier et al., 2004; Möbius et al., 2002; White et al., 2006).”
Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication (2013, methodology): “We utilized the neutral sphingomyelinase inhibitor GW4869, which inhibits the release of exosomes [42].”