Epsin 1 is Involved in Recruitment of Ubiquitinated EGF Receptors into Clathrin-Coated Pits |
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| Authors: | Maja Kazazic Vibeke Bertelsen Ketil Winther Pedersen Tram Thu Vuong Michael Vibo Grandal Marianne Skeie Rødland Linton M Traub Espen Stang Inger Helene Madshus |
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| Institution: | Institute of Pathology, University of Oslo, Rikshospitalet HF, N-0027 Oslo, Norway;
Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark;
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA15261, USA;
Division of Pathology, Rikshospitalet University Hospital, Oslo, Norway |
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| Abstract: | Epsin consists of an epsin NH2-terminal homology domain that promotes interaction with phospholipids, several AP-2-binding sites, two clathrin-binding sequences and several Eps15 homology domain-binding motifs. Epsin additionally possesses ubiquitin-interacting motifs (UIMs) and has been demonstrated to bind ubiquitinated cargo. We therefore investigated whether epsin promoted clathrin-mediated endocytosis of the ubiquitinated EGF receptor (EGFR). By immunoprecipitation, we found that epsin 1 interacted with ubiquitinated EGFR and that functional UIMs were essential for complex formation. Furthermore, RNA interference-mediated knockdown of epsin 1 was found to inhibit internalization of the EGFR, while having no effect on endocytosis of the transferrin receptor. Additionally, upon knockdown of epsin 1, translocation of the EGFR to central parts of clathrin-coated pits was inhibited. This supports the contention that epsin 1 promotes endocytosis of the ubiquitinated EGFR. |
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| Keywords: | AP-2 clathrin-coated pit EGF receptor epsin ubiquitin |
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