Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation

  • J Biol Chem. 2007 Mar 30;282(13):9805-9812. doi: 10.1074/jbc.M611635200.
Yu May Ma  1 ,  Emmanuel Boucrot  1 ,  Judit Villén  2 ,  El Bachir Affar  3 ,  Steven P Gygi  2 ,  Heinrich G Göttlinger  4 ,  Tomas Kirchhausen  5
Affiliations
  • 1. CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
  • 2. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
  • 3. Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
  • 4. Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
  • 5. CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115. Electronic address: [email protected].
PMID: 17261583 DOI: 10.1074/jbc.M611635200
Abstract

To reach the lysosomes, down-regulated receptors such as the epidermal growth factor receptor must first be sorted into internal vesicles of late endosomes (multivesicular bodies), a ubiquitin-dependent event that requires the coordinated function of the endosome sorting complex required for transport (ESCRT) proteins. Here we report that CHMP3, an ESCRT-III complex component, and associated molecule of SH3 domain of STAM (AMSH), a deubiquitinating enzyme, interact with each Other in cells. A dominant-negative version of CHMP3, which specifically prevents targeting of AMSH to endosomes, inhibits degradation but not internalization of EGFR, suggesting that endosomal AMSH is a functional component of the multivesicular body pathway.