A vital sugar code for ricin toxicity

• Verfasst von: Taubenschmid, Jasmin [VerfasserIn]
• Verfasst von: Jost, Markus [VerfasserIn]
• Verfasst von: Thiel, Christian [VerfasserIn]
• Verfasst von: Körner, Christian [VerfasserIn]
• Titel: A vital sugar code for ricin toxicity
• Verf.angabe: Jasmin Taubenschmid, Johannes Stadlmann, Markus Jost, Tove Irene Klokk, Cory D. Rillahan, Andreas Leibbrandt, Karl Mechtler, James C. Paulson, Julian Jude, Johannes Zuber, Kirsten Sandvig, Ulrich Elling, Thorsten Marquardt, Christian Thiel, Christian Koerner, Josef M. Penninger
• Umfang: 14 S.
• Fussnoten: Published online 19 September 2017 ; Gesehen am 13.07.2018
• Titel Quelle: Enthalten in: Cell research
• Jahr Quelle: 2017
• Band/Heft Quelle: 27(2017), 11, S. 1351-1364
• ISSN Quelle: 1748-7838
• DOI: doi:10.1038/cr.2017.116
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577593162

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.