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Ceramide triggers budding of exosome vesicles into multivesicular endosomes


Trajkovic, K; Hsu, C; Chiantia, S; Rajendran, L; Wenzel, D; Wieland, F; Schwille, P; Brügger, B; Simons, M (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 319(5867):1244-1247.

Abstract

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.

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.

Citations

630 citations in Web of Science®
650 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:19 Oct 2011 12:10
Last Modified:05 Apr 2016 15:02
Publisher:American Association for the Advancement of Science (AAAS)
ISSN:0036-8075
Publisher DOI:10.1126/science.1153124
PubMed ID:18309083

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