Trichosanthin Interacts with and Enters Cells via LDL Receptor Family Members

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 th...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-04, Vol.270 (2), p.453-457
Main Authors: Chan, Wah-Lun, Shaw, Pang-Chui, Tam, Siu-Cheung, Jacobsen, Christian, Gliemann, Jørgen, Nielsen, Morten S.
Format: Article
Language:English
Subjects:
AIDS/HIV
choriocarcinoma cells
Endocytosis
Flow Cytometry
Heymann Nephritis Antigenic Complex
Humans
lipoprotein (low density) receptors
Low Density Lipoprotein Receptor-Related Protein-1
megalin
Membrane Glycoproteins - metabolism
receptor binding
receptor-associated protein
receptor-associated proteins
Receptors, Immunologic - metabolism
Receptors, LDL - metabolism
ribosome-inactivating protein
Surface Plasmon Resonance
the α2-macroglobulin receptor/LDL receptor-related protein
trichosanthin
Trichosanthin - metabolism
Tumor Cells, Cultured
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.2441