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Pathways followed by protein toxins into cells
Kirsten Sandvig1, Bjørn Spilsberg, Silje U Lauvrak
1Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway. ksandvig@radium.uio.no
International Journal of Medical Microbiology : IJMM
|May 20, 2004
Summary
This study examines how protein toxins like ricin, Shiga, and cholera toxin travel within cells. Understanding their retrograde transport to the endoplasmic reticulum (ER) reveals insights into cellular pathways.
Area of Science:
- Cell Biology
- Molecular Biology
- Toxicology
Background:
- Protein toxins possess enzymatically active domains targeting cytosolic components.
- Certain toxins, including ricin, Shiga toxin, and cholera toxin, utilize a specific cellular entry and transport pathway.
Purpose of the Study:
- To investigate the intracellular transport pathways of ricin, Shiga toxin, and cholera toxin.
- To elucidate the molecular mechanisms underlying retrograde transport of toxins to the endoplasmic reticulum (ER).
Main Methods:
- Analysis of toxin entry, endocytosis, and retrograde transport mechanisms.
- Comparative study of ricin, Shiga toxin, and cholera toxin pathways.
Main Results:
- Toxins are endocytosed and transported retrogradely to the ER before cytosolic translocation.
- Retrograde transport involves Rab and SNARE proteins, cytosolic calcium, phosphatidylinositol 3-kinase, and cholesterol.
- Differences in toxin transport suggest multiple pathways or differential regulation between early endosomes and the Golgi apparatus.
Conclusions:
- Studying these toxins provides valuable information on intracellular transport pathways.
- The ER serves as a critical point for the translocation of enzymatically active toxin domains into the cytosol.
- Distinct transport dynamics among toxins indicate complex regulatory mechanisms governing intracellular trafficking.