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A vital sugar code for ricin toxicity
A vital sugar code for ricin toxicity
- Source :
- Cell Research
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no antidote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter Slc35c1 and fucosyltransferase Fut9 are key regulators of ricin toxicity. Genetic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intracellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin. Mechanistically, we confirm that reduced fucosylation leads to increased sialylation of Lewis X structures and thus masking of ricin-binding sites. Inactivation of the sialyltransferase responsible for modifications of Lewis X (St3Gal4) increases the sensitivity of cells to ricin, whereas its overexpression renders cells more resistant to the toxin. Thus, we have provided unprecedented insights into an evolutionary conserved modular sugar code that can be manipulated to control ricin toxicity.
- Subjects :
- 0301 basic medicine
endocrine system
Fucosyltransferase
Monosaccharide Transport Proteins
intracellular trafficking
Sialyltransferase
Golgi Apparatus
Ricin
Mice
sialylation
03 medical and health sciences
chemistry.chemical_compound
symbols.namesake
Animals
Humans
toxin
Molecular Biology
Fucosylation
biology
Membrane Transport Proteins
Transporter
Cell Biology
Golgi apparatus
Fucosyltransferases
Sialyltransferases
carbohydrates (lipids)
enzymes and coenzymes (carbohydrates)
030104 developmental biology
chemistry
Biochemistry
Lewis X
Mutation
Toxicity
fucosylation
biology.protein
symbols
Original Article
Gene Deletion
Intracellular
Subjects
Details
- ISSN :
- 17487838 and 10010602
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Cell Research
- Accession number :
- edsair.doi.dedup.....76ed7ed4bf947ca70a06848daece062b
- Full Text :
- https://doi.org/10.1038/cr.2017.116