Question:
Where does the saporin payload release after internalization? For example, does it require trafficking into a late endosome/lysosomal compartment?
Answer:
Thank you for reaching out to us. Hopefully I can help answer some of your questions regarding what happens to saporin after being internalized.
I would first like to refer you to an article we published, titled “Streptavidin-Saporin: Converting Biotinylated Materials into Targeted Toxins”. In it we review the internalization of saporin and include a few references for support. To answer your question in general, yes the conjugate is typically endocytosed and makes its way to the late endosome.
As an overview of this debated topic, the Wensley, H.J. et al 2019 article (ref #4) studied the escape of saporin from the late endosome and examined the endocytic process to quantify the endosomal escape into the cytosol. The Holmes, S.E et al 2015 (ref #5) and Giansanti, F. et al 2018 (ref #6) articles describe additional research examining chemical and genetic strategies used in assisting in saporin’s escape from the endosome. After endocytocis, Vago, R. et al 2005 (ref #7) compared saporin and ricin A chain and other bacterial toxins looking at their different intracellular routes to enter the cytosol. These articles should provide a nice foundation and hopefully better answer any questions.
If you’re interested in visualizing lysosomal trafficking, you might consider our pHast product line. These are secondary pH-dependent fluorescent conjugates, meaning that they only fluoresce once inside the endosomes and lysosomes of cells (which are acidic compared to the cytosol).
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