Lipid requirements for entry of protein toxins into cells.
The plant toxin ricin and the bacterial toxin Shiga toxin both belong to a group of protein toxins having one moiety that binds to the cell surface, and another, enzymatically active moiety, that enters the cytosol and inhibits protein synthesis by inactivating ribosomes. Both toxins travel all the way from the cell surface to endosomes, the Golgi apparatus and the ER before the ribosome-inactivating moiety enters the cytosol. Shiga toxin binds to the neutral glycosphingolipid Gb3 at the cell surface and is therefore dependent on this lipid for transport into the cells, whereas ricin binds both glycoproteins and glycolipids with terminal galactose. The different steps of transport used by these toxins have specific requirements for lipid species, and with the recent developments in mass spectrometry analysis of lipids and microscopical and biochemical dissection of transport in cells, we are starting to see the complexity of endocytosis and intracellular transport. In this article we describe lipid requirements and the consequences of lipid changes for the entry and intoxication with ricin and Shiga toxin. These toxins can be a threat to human health, but can also be exploited for diagnosis and therapy, and have proven valuable as tools to study intracellular transport.
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway. Electronic address: ksandvig@radium.uio.no.
Kirsten
K
Sandvig
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: jonas.bergan@rr-research.no.
Jonas
J
Bergan
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Department of Biosciences, University of Oslo, Oslo, Norway. Electronic address: simona.kavaliauskiene@rr-research.no.
Simona
S
Kavaliauskiene
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: tore.skotland@rr-research.no.
Tore
T
Skotland
D000818:Animals; D002477:Cells / Q000166:cytology / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D050356:Lipid Metabolism; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D014118:Toxins, Biological / Q000378:metabolism*
D011506:Proteins; D014118:Toxins, Biological
Cholesterol; Endocytosis; Gb3; Glycosphingolipids; Golgi; Sphingomyelin