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Toxins 2016, 8(3), 67;

Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes

Keenan Research Centre for Biomedical Science, St. Michael′s Hospital, 209 Victoria Street, 6th Floor, Toronto, ON M5S 1T8, Canada
Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
Institute for Biomedical Engineering and Science Technology (IBEST), Ryerson University and St. Michael′s Hospital, Toronto, ON M5B 2K3, Canada
Current address: Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Toon, Ehime 791-0295, Japan
Author to whom correspondence should be addressed.
Academic Editors: Harald Genth and Michel R. Popoff
Received: 4 February 2016 / Revised: 26 February 2016 / Accepted: 26 February 2016 / Published: 8 March 2016
Full-Text   |   PDF [1288 KB, uploaded 8 March 2016]   |  


Cholesterol is an essential structural component of cellular membranes in eukaryotes. Cholesterol in the exofacial leaflet of the plasma membrane is thought to form membrane nanodomains with sphingolipids and specific proteins. Additionally, cholesterol is found in the intracellular membranes of endosomes and has crucial functions in membrane trafficking. Furthermore, cellular cholesterol homeostasis and regulation of de novo synthesis rely on transport via both vesicular and non-vesicular pathways. Thus, the ability to visualize and detect intracellular cholesterol, especially in the plasma membrane, is critical to understanding the complex biology associated with cholesterol and the nanodomains. Perfringolysin O (PFO) theta toxin is one of the toxins secreted by the anaerobic bacteria Clostridium perfringens and this toxin forms pores in the plasma membrane that causes cell lysis. It is well understood that PFO recognizes and binds to cholesterol in the exofacial leaflets of the plasma membrane, and domain 4 of PFO (D4) is sufficient for the binding of cholesterol. Recent studies have taken advantage of this high-affinity cholesterol-binding domain to create a variety of cholesterol biosensors by using a non-toxic PFO or the D4 in isolation. This review highlights the characteristics and usefulness of, and the principal findings related to, these PFO-derived cholesterol biosensors. View Full-Text
Keywords: cholesterol; perfringolysin O; biosensor; membranes; microscopy cholesterol; perfringolysin O; biosensor; membranes; microscopy

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Maekawa, M.; Yang, Y.; Fairn, G.D. Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes. Toxins 2016, 8, 67.

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