title: Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation.
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.
authors.affiliation: CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Yu May
authors.initials: YM
authors.lastname: Ma
authors.affiliation: CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Boucrot
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Judit
authors.initials: J
authors.lastname: Villén
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: El Bachir
authors.initials: EB
authors.lastname: Affar
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gygi
authors.affiliation: Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, Massachusetts 01605.
authors.forename: Heinrich G
authors.initials: HG
authors.lastname: Göttlinger
authors.affiliation: 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.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhausen
mesh_terms: 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*
chemical_list: 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