A vital sugar code for ricin toxicity  

作　　者：Jasmin Taubenschmld Johannes Stadlmann Markus Jost Tove Irene Klok.k 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 

机构地区：[1]MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, VBC - Vienna BioCenter Campus, Dr Bohr- Gasse 3, 1030 Vienna, Austria [2]Universitdtsklinikum Heidelberg, Zentrum fur Kinderund Jugendmedizin, Analysezentrum III, Klinik fiir Kinderheilkunde I, Im Neuenheimer Feld 669, 69120 Heidelberg, Germany [3]Department of Molecular Cell Biology and Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Mon- tebello, 0379 Oslo, Norway [4]Departments of Cell and Molecular Biology, Chemical Physiology, and Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA [5]Institute of Molecular Pathology (IMP), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria [6]Department of Biosciences, University of Oslo, 0316 Oslo, Norway [7]Universitcitsklinikum Mioster, Klinik fur Kinderheilkunde, Albert-Schweitzer-Campus 1, 48149 Munster, Germany

出　　处：《Cell Research》2017年第11期1351-1364,共14页细胞研究（英文版）

摘　　要：Ricin is one of the most feared bioweapons in the world due to its extreme toxicity and easy access. Since no anti- dote exists, it is of paramount importance to identify the pathways underlying ricin toxicity. Here, we demonstrate that the Golgi GDP-fucose transporter S1c35cl and fucosyltransferase Fut9 are key regulators of ricin toxicity. Ge- netic and pharmacological inhibition of fucosylation renders diverse cell types resistant to ricin via deregulated intra- cellular trafficking. Importantly, cells from a patient with SLC35C1 deficiency are also resistant to ricin. Mechanis- tically, 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 pro- vided unprecedented insights into an evolutionary conserved modular sugar code that can be manipulated to control ricin toxicity.

关 键 词：RICIN TOXIN FUCOSYLATION SIALYLATION Lewis X intracellular trafficking 

分 类 号：Q[生物学]