There is increasing evidence that ubiquitination of receptors provides an important endosomal sorting signal. Here we report that mammalian class E vacuolar protein-sorting (vps) proteins recognize ubiquitin. Both tumor susceptibility gene 101 (TSG101)/human VPS (hVPS)28 and hepatocyte growth factor receptor substrate (Hrs) cytosolic complexes bind ubiquitin-agarose. TSG101 and hVPS28 are localized to endosomes that contain internalized EGF receptor and label strongly for ubiquitinated proteins. Microinjection of anti-hVPS28 specifically retards EGF degradation and leads to endosomal accumulation of ubiquitin–protein conjugates. Likewise, depletion of TSG101 impairs EGF trafficking and causes dramatic relocalization of ubiquitin to endocytic compartments. Similar defects are found in cells overexpressing Hrs, further emphasizing the links between class E protein function, receptor trafficking, and endosomal ubiquitination.
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1 April 2002
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March 26 2002
Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein–ubiquitin conjugates
Naomi Bishop,
Naomi Bishop
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Alistair Horman,
Alistair Horman
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
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Philip Woodman
Philip Woodman
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Search for other works by this author on:
Naomi Bishop
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Alistair Horman
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Philip Woodman
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom
Address correspondence to Philip Woodman, University of Manchester, Oxford Rd., Manchester M13 9PT, UK. Tel.: 44-161-275-7846. Fax: 44-161-275-5082. E-mail: [email protected]
N. Bishop and A. Horman contributed equally to this work.
*
Abbreviations used in this paper: EEA1, early endosome-associated antigen 1; EGFR, EGF receptor; GSH, glutathione; Hrs, hepatocyte growth factor receptor substrate; hVPS, human VPS; mHrs, mouse Hrs; siRNA, small interfering RNA; TSG101, tumor susceptibility gene 101; Ubc, ubiquitin-conjugating; UIM, ubiquitin-interacting motif; VPS, vacuolar protein sorting.
Received:
December 17 2001
Revision Received:
February 15 2002
Accepted:
February 19 2002
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2002
J Cell Biol (2002) 157 (1): 91–102.
Article history
Received:
December 17 2001
Revision Received:
February 15 2002
Accepted:
February 19 2002
Citation
Naomi Bishop, Alistair Horman, Philip Woodman; Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein–ubiquitin conjugates . J Cell Biol 1 April 2002; 157 (1): 91–102. doi: https://doi.org/10.1083/jcb.200112080
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