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The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins

Abstract

Selective trafficking of membrane proteins to lysosomes for destruction is required for proper cell signalling and metabolism. Ubiquitylation aids this process by specifying which proteins should be transported to the lysosome lumen by the multivesicular endosome pathway. The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes. Then, through a highly conserved mechanism also used in cytokinesis and viral budding, it mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane. The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell.

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Figure 1: Endocytic internalization and sorting.
Figure 2: Composition and molecular interactions of the ESCRT machinery.
Figure 3: The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.
Figure 4: Involvement of the ESCRT machinery in three topologically equivalent types of membrane abscission.

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Acknowledgements

C.R. is a postdoctoral fellow of the Norwegian Cancer Society. We also thank the Research Council of Norway, the Novo-Nordisk Foundation and the Hartmann Family Foundation for supporting our research.

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Correspondence should be addressed to H.S. (stenmark@ulrik.uio.no).

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Raiborg, C., Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445–452 (2009). https://doi.org/10.1038/nature07961

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