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Science 29 February 2008:
Vol. 319. no. 5867, pp. 1244 - 1247
DOI: 10.1126/science.1153124
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Reports

Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes

Katarina Trajkovic,1,2* Chieh Hsu,1,2* Salvatore Chiantia,5 Lawrence Rajendran,6 Dirk Wenzel,3 Felix Wieland,4 Petra Schwille,5 Britta Brügger,4 Mikael Simons1,2,7{dagger}

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.

1 Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, 37073 Göttingen, Germany.
2 Max-Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany.
3 Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
4 Heidelberg University Biochemistry Center, 69120 Heidelberg, Germany.
5 BioTec, TU Dresden, 01307 Dresden, Germany.
6 Max-Planck-Institute of Cell Biology and Genetics, 01307 Dresden, Germany.
7 Department of Neurology, University of Göttingen, 37073 Göttingen, Germany.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: msimons{at}gwdg.de

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular Mechanisms of Soluble Cytokine Receptor Generation.
S. J. Levine (2008)
J. Biol. Chem. 283, 14177-14181
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Science. ISSN 0036-8075 (print), 1095-9203 (online)