title: Trichosanthin interacts with and enters cells via LDL receptor family members.
abstract: The type-I ribosome-inactivating protein trichosanthin displays selective cytotoxicity, suggesting specific mechanisms for entry into cells. Here we show that trichosanthin binds specifically to the endocytic receptors LRP and megalin, and that binding as well as uptake into cells is inhibited by the receptor-associated protein (RAP). The results suggest that the known abortifacient and renotoxic actions of trichosanthin are caused by LRP-mediated uptake in trophoblasts and megalin-mediated uptake in proximal tubule epithelial cells, respectively.
authors.affiliation: Department of Physiology, Department of Biochemistry, Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Chan
authors.forename: P C
authors.initials: PC
authors.lastname: Shaw
authors.forename: S C
authors.initials: SC
authors.lastname: Tam
authors.forename: C
authors.initials: C
authors.lastname: Jacobsen
authors.forename: J
authors.initials: J
authors.lastname: Gliemann
authors.forename: M S
authors.initials: MS
authors.lastname: Nielsen
mesh_terms: D004705:Endocytosis; D005434:Flow Cytometry; D026541:Heymann Nephritis Antigenic Complex; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D015978:Trichosanthin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D026541:Heymann Nephritis Antigenic Complex; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D015978:Trichosanthin