Cell Biology

Membrane Sorting

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Science  15 Mar 2002:
Vol. 295, Issue 5562, pp. 1975
DOI: 10.1126/science.295.5562.1975a

Endocytosis is the process by which cells take up materials such as nutrients, hormones, and growth factors from the outside milieu into membrane-bound intracellular compartments, known as endosomes. The receptors for these materials are then trucked to the degradative organelle of the cell, the lysosome, or recycled to the cell surface. In some systems, modification of membrane proteins by ubiquitin has been linked to uptake and endocytic traffic. Ubiquitin is added to target proteins by ubiquitin ligases and can be removed by the proteasome, which can either remove ubiquitin groups or degrade the entire protein.

Longva et al. and Bishop et al. describe their independent analyses of factors controlling the trafficking of epidermal growth factor (EGF) and its receptor after internalization. After binding EGF, the EGF receptor becomes internalized. Prolonged administration of EGF causes some ubiquitination of the receptor and correlates with the recruitment of the ubiquitin ligase c-Cbl to the EGF-containing endosomes. The ubiquitination of the EGF receptor-containing endosomes appears to recruit a protein important in lysosomal targeting termed Vps28. When Vps28 antibodies were microinjected into cells, EGF degradation was retarded, and ubiquitin conjugates accumulated in the endosomes. These findings extend and confirm findings by van Kerkhof et al., who have found that proteasome inhibitors blocked a late step in lysosomal transport of membrane proteins without affecting the trafficking of soluble proteins. — SMH

J. Cell Biol. 156, 843 (2002); J. Cell Biol., in press; Mol. Biol. Cell12, 2556 (2001).

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