Related Experiment Videos
Trichosanthin interacts with and enters cells via LDL receptor family members
1Department of Physiology, Department of Biochemistry, Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
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.
Insights
Trichosanthin, a cytotoxic protein, enters cells via specific endocytic receptors. Its harmful effects are linked to low-density lipoprotein receptor (LRP) and megalin-mediated uptake in different cell types.
Area of Science:
- Cell Biology
- Toxicology
- Protein Biochemistry
Background:
- Type-I ribosome-inactivating proteins, like trichosanthin, exhibit selective cytotoxicity.
- The cellular entry mechanisms of trichosanthin are not fully understood.
- Specific cellular uptake pathways are suggested by its cytotoxic profile.
Purpose of the Study:
- To elucidate the specific cell entry mechanisms of trichosanthin.
- To identify the cellular receptors involved in trichosanthin uptake.
- To correlate receptor-mediated uptake with trichosanthin's known toxic effects.
Main Methods:
- Investigated trichosanthin binding to endocytic receptors.
- Utilized receptor-associated protein (RAP) to inhibit receptor binding and uptake.
- Examined LRP-mediated uptake in trophoblasts and megalin-mediated uptake in proximal tubule epithelial cells.
Main Results:
- Trichosanthin specifically binds to low-density lipoprotein receptor (LRP) and megalin.
- Receptor-associated protein (RAP) significantly inhibits trichosanthin binding and cellular uptake.
- Evidence suggests LRP mediates uptake in trophoblasts and megalin in proximal tubule cells.
Conclusions:
- Trichosanthin utilizes LRP and megalin for cellular entry.
- LRP-mediated uptake in trophoblasts likely causes abortifacient effects.
- Megalin-mediated uptake in proximal tubule cells likely causes renotoxic effects.