Malerød and Pedersen with cover story in Traffic.

Pedersen (l.) and Malerřd
The cover of the September 2011 issue of the journal Traffic displays 3D-reconstructions of endosomes recorded by two postdocs in Harald Stenmark's group at the Institute for Cancer Research and Centre for Cancer Biomedicine, Lene Malerød and Nina Marie Pedersen (Malerød is now senior scientist in Trond Lehren's group at Department of Medical Genetics).
The cover image is taken from the paper "Cargo-dependent degradation of ESCRT-I as a feedback mechanism to modulate endosomal sorting", which deals with a topic of significant interest in cancer research, namely the fact that many cell-surface proteins, including growth factor receptors, are internalized and degraded in response to ligand binding.

Previous work in Stenmark's lab has revealed that the endosomal sorting complex required for transport (ESCRT) machinery is central in epidermal growth factor (EGF)-induced degradation of EGF receptors. This machinery consists of four complexes termed ESCRT-0, -I, -II and -III, which recognize ubiquitinated membrane proteins in endosome membranes and sort them into the endosome lumen and thereby commit the proteins for lysosomal degradation (reviewed by Raiborg and Stenmark, Nature 2009. Malerød and Pedersen made the surprising observation that one of the ESCRT complexes, ESCRT-I, follows its cargo into the endosome lumen and gets degraded along with its cargo. The authors speculated about possible advantages of such stimulus-induced degradation of the endosomal sorting machinery and came up with evidence that this mechanism represents a novel feedback control of cell signalling that prevents general degradation of cell surface receptors as consequence of stimulation of one specific pathway. The work was a collaboration with two other groups within the Centre for Cancer Biomedicine, those of Edgar Rivedal and Knut Liestøl.


Cargo-Dependent Degradation of ESCRT-I as a Feedback Mechanism to Modulate Endosomal Sorting.
Malerød L, Pedersen NM, Sem Wegner CE, HÊlène Lobert V, Leithe E, Brech A, Rivedal E, Liestøl K, Stenmark H.
Traffic. 2011 Sep;12(9):1211-26.

The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.
Raiborg C, Stenmark H.
Nature. 2009 Mar 26;458(7237):445-52. Review.

Web page of Harald Stenmark's group

Department of Biochemistry

Institute for Cancer Research

The cover of Traffic shows 3D-reconstructions of cross-sections of large endosomes (green) labelled for ESCRT-0 (top left), ESCRT-I (top right), ESCRT-II (bottom left) and ESCRT-III (bottom right). Note that whereas ESCRT-0, -II and -III are associated with the limiting membrane of the endosome, ESCRT-I is present in the lumen.

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