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Hrs recruits clathrin to early endosomes
Author(s) -
Raiborg Camilla,
Grønvold Bache Kristi,
Mehlum Anja,
Stang Espen,
Stenmark Harald
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.17.5008
Subject(s) - endosome , clathrin , endocytosis , endocytic cycle , microbiology and biotechnology , biology , phosphatidylinositol , wortmannin , pleckstrin homology domain , signal transduction , intracellular , biochemistry , receptor
The hepatocyte growth factor‐regulated tyrosine kinase substrate, Hrs, has been implicated in intracellular trafficking and signal transduction. Hrs contains a phosphatidylinositol 3‐phosphate‐binding FYVE domain that contributes to its endosomal targeting. Here we show that Hrs and EEA1, a FYVE domain protein involved in endocytic membrane fusion, are localized to different regions of early endosomes. We demonstrate that Hrs co‐localizes with clathrin, and that the C‐terminus of Hrs contains a functional clathrin box motif that interacts directly with the terminal β‐propeller domain of clathrin heavy chain. A massive recruitment of clathrin to early endosomes was observed in cells transfected with Hrs, but not with Hrs lacking the C‐terminus. Furthermore, the phosphatidylinositol 3‐kinase inhibitor wortmannin caused the dissociation of both Hrs and clathrin from endosomes. While overexpression of Hrs did not affect endocytosis and recycling of transferrin, endocytosed epidermal growth factor and dextran were retained in early endosomes. These results provide a molecular mechanism for the recruitment of clathrin onto early endosomes and suggest a function for Hrs in trafficking from early to late endosomes.