Delivery into cells: lessons learned from plant and bacterial toxins

Area of Science:

• Cell Biology
• Molecular Biology
• Toxicology

Background:

• Protein toxins from bacteria and plants often target the cell's cytosol.
• Understanding toxin entry mechanisms provides insights into endocytosis and intracellular sorting.
• Toxins can possess distinct binding (B-moiety) and enzymatic (A-moiety) components, or only the active moiety.

Purpose of the Study:

• To review the mechanisms of protein toxin entry into the cytosol.
• To discuss the utility of toxins as vectors for intracellular delivery.
• To highlight how toxins aid in studying endosomal escape and cellular transport.

Main Methods:

• Review of established bacterial toxins (e.g., Shiga toxin, diphtheria toxin) and plant toxins (e.g., ricin, gelonin).
• Analysis of toxin entry pathways, including endosomal pH-dependent release and Golgi-ER-cytosol transport.
• Discussion of toxins lacking a binding moiety (e.g., gelonin) for studying endosomal membrane disruption.

Main Results:

• Toxins with binding moieties can be engineered as vectors to translocate various molecules into the cytosol.
• Cytosolic entry routes vary: some toxins exit endosomes, while others traffic through the Golgi and ER.
• Toxins without binding moieties, though less toxic initially, are valuable tools for probing endosomal escape.

Conclusions:

• Protein toxins are invaluable tools for elucidating cellular transport and translocation processes.
• Toxins serve as effective vectors for delivering molecules into the cell's interior.
• Investigating toxin mechanisms enhances understanding of endocytosis, intracellular sorting, and targeted drug delivery strategies.