Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation.
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.
Ma
Yu May
YM
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Boucrot
Emmanuel
E
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Villén
Judit
J
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Affar
El Bachir
EB
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Gygi
Steven P
SP
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
Göttlinger
Heinrich G
HG
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
Kirchhausen
Tomas
T
CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115. Electronic address: Kirchhausen@crystal.harvard.edu.
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000201:enzymology* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
C498543:CHMP3 protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; C486696:STAMBP protein, human; D066246:ErbB Receptors; D043222:Ubiquitin Thiolesterase