Escorting receptors for degradation

Lene Malerd
In a recent paper in Traffic, Lene Malerød, a postdoc in Stenmark’s lab, shows that the ESCRT-II complex is required for degradation of ubiquitinated epidermal growth factor receptor and chemokine receptors. This provides new insight into how growth factor and chemokine receptors are transported intracellularly and identifies a novel potential tumour suppressor complex.
Binding of growth factors and cytokines to their cognate receptors on cell membranes triggers their endocytosis and degradation in lysosomes, thus providing a physiologically important negative feedback mechanism for cell signalling.

The ESCRT-II complex recognizes ubiquitinated receptors in the endosomal membrane, thus initiating their sorting to degradative lysosomes. (click to enlarge image)
The ESCRT-II complex recognizes ubiquitinated receptors in the endosomal membrane, thus initiating their sorting to degradative lysosomes. (click to enlarge image)
It is not known in detail how endocytosed receptors are trafficked to the degradative lysosomes, but work in Harald Stenmark’s lab has uncovered several factors involved in this process. Among these are the so-called endosomal sorting complexes required for transport (ESCRTs), and Thomas Slagsvold in Stenmark’s group has previously shown that the so-called GLUE domain in the ESCRT-II complex binds ubiquitin .

In a recent paper in Traffic, Lene Malerød, a postdoc in Stenmark’s lab, shows that the ESCRT-II complex is required for degradation of ubiquitinated epidermal growth factor receptor and chemokine receptors. This provides new insight into how growth factor and chemokine receptors are transported intracellularly and identifies a novel potential tumour suppressor complex.

Links:

Malerod L, Stuffers S, Brech A, Stenmark H.
Vps22/EAP30 in ESCRT-II Mediates Endosomal Sorting of Growth Factor and Chemokine Receptors Destined for Lysosomal Degradation.
Traffic. 2007 Aug 20 [Epub ahead of print]

Lene Malerød

The home page of Harald Stenmark's group (radium.no/stenmark)

Department of Biochemistry

Institute of Cancer Research
 
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