Pawar, Vidya, De, Antara, Briggs, Laura, Omar, Mahmoud M., Sweeney, Sean T., Lord, Mike, Roberts, L. M. (Lynne M.), Spooner, Robert A. and Moffat, Kevin G. (2011) RNAi screening of Drosophila (Sophophora) melanogaster S2 cells for ricin sensitivity and resistance. Journal of Biomolecular Screening, Vol.16 (No.4). pp. 436-442. doi:10.1177/1087057110397890

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Abstract

The ribosome-inhibiting toxin ricin binds exposed β1→4 linked galactosyls on multiple glycolipids and glycoproteins on the cell surface of most eukaryotic cells. After endocytosis, internal cell trafficking is promiscuous, with only a small proportion of ricin proceeding down a productive (cytotoxic) trafficking route to the endoplasmic reticulum (ER). Here, the catalytic ricin A chain traverses the membrane to inactivate the cytosolic ribosomes, which can be monitored by measuring reduction in protein biosynthetic capacity or cell viability. Although some markers have been discovered for the productive pathway, many molecular details are lacking. To identify a more comprehensive set of requirements for ricin intoxication, the authors have developed an RNAi screen in Drosophila S2 cells, screening in parallel the effects of individual RNAi treatments alone and when combined with a ricin challenge. Initial screening of 806 gene knockdowns has revealed a number of candidates for both productive and nonproductive ricin trafficking, including proteins required for transport to the Golgi, plus potential toxin interactors within the ER and cytosol.

Item Type:	Journal Article
Subjects:	Q Science > QL Zoology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Drosophila melanogaster -- Genetics, Ricin -- Physiological effect
Journal or Publication Title:	Journal of Biomolecular Screening
Publisher:	Sage Publications, Inc.
ISSN:	1087-0571
Official Date:	April 2011
Dates:	Date Event April 2011 Published
Volume:	Vol.16
Number:	No.4
Page Range:	pp. 436-442
DOI:	10.1177/1087057110397890
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Great Britain. Dept. of Health (DoH), Great Britain. Home Office, Medical Research Council (Great Britain) (MRC), National Institutes of Health (U.S.) (NIH), Wellcome Trust (London, England)
Grant number:	G0400580 (MRC), 5U01AI65869-02 (NIH), 080566/Z/06/Z (WT)

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