title: Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus.
abstract: During clathrin-mediated endocytosis, adaptor proteins recognize specific internalization signals on cargo receptors, either recruiting cargos into clathrin-coated pits (CCPs) or initiating clathrin-coat assembly around the cargo molecules. Here, we identify epsin 1, a clathrin-, ubiquitin-, and phospholipid-interacting protein, as a cargo-specific adaptor for influenza virus entry through the clathrin-mediated pathway. Using live-cell imaging to monitor the entry of individual virus particles, we observed recruitment of epsin 1 to the binding sites of influenza viruses in synchrony with the assembly of CCPs. Epsin 1 knockdown by siRNA significantly inhibited the clathrin-mediated endocytosis of the influenza virus and caused the majority of the virus particles to enter through a clathrin-independent pathway. The same treatment did not affect the entry of several classical ligands for clathrin-mediated endocytosis, including transferrin, LDL, and EGF. Overexpression of the dominant-negative epsin 1 mutant lacking the ubiquitin-interaction motifs nearly completely blocked the clathrin-mediated entry of the influenza virus without affecting transferrin uptake. These results suggest that epsin 1 functions as a cargo-specific adaptor for the clathrin-mediated entry of the influenza virus.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D009975:Orthomyxoviridae / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D014168:Transferrin / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008078:Cholesterol, LDL; D002966:Clathrin; D034741:RNA, Small Interfering; D014168:Transferrin; C114154:epsin; D004815:Epidermal Growth Factor