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Clathrin anchors deubiquitinating enzymes, AMSH and AMSH‐like protein, on early endosomes
Author(s) -
Nakamura Michihiko,
Tanaka Nobuyuki,
Kitamura Naomi,
Komada Masayuki
Publication year - 2006
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2006.00963.x
Subject(s) - endosome , deubiquitinating enzyme , clathrin , biology , microbiology and biotechnology , ubiquitin , endocytosis , biochemistry , receptor , gene , intracellular
Endosomal sorting of ubiquitinated membrane proteins for trafficking to lysosomes is executed by a complex of two ubiquitin‐binding proteins, Hrs and STAM, that localizes on a microdomain of early endosomes with a flat clathrin coat. AMSH is a deubiquitinating enzyme that interacts with STAM and is implicated in the down‐regulation of epidermal growth factor receptor. AMSH has a close homolog, AMSH‐like protein (AMSH‐LP). Here we show that AMSH‐LP is also a deubiquitinating enzyme that acts on early endosomes. We further show that AMSH and AMSH‐LP bind to the terminal domain of clathrin heavy chain via a novel clathrin‐binding site conserved between these proteins. Exogenously expressed AMSH and AMSH‐LP co‐localized with clathrin on early endosomes. However, deletion of the clathrin‐binding site from the proteins, as well as RNA interference‐mediated depletion of clathrin heavy chain, resulted in a failure of AMSH and AMSH‐LP to localize on endosomes. In contrast, a mutant of AMSH that lacks the ability to bind STAM localized normally on endosomes. We suggest that AMSH and AMSH‐LP are anchored on the early endosomal membrane via interaction with the clathrin coat.