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doi:10.22028/D291-27869
Titel: | Adapting Yeast as Model to Study Ricin Toxin A Uptake and Trafficking |
VerfasserIn: | Becker, Björn Schmitt, Manfred J. |
Sprache: | Englisch |
Titel: | Toxins |
Bandnummer: | 3 |
Heft: | 7 |
Startseite: | 834 |
Endseite: | 847 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2011 |
Freie Schlagwörter: | ricin toxin A chain ER retention signal yeast spheroplasts toxin endocytosis and transport oyxgen-sensor microtiter plate H/KDEL |
DDC-Sachgruppe: | 570 Biowissenschaften, Biologie |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | The plant A/B toxin ricin represents a heterodimeric glycoprotein belonging to the family of ribosome inactivating proteins, RIPs. Its toxicity towards eukaryotic cells results from the depurination of 28S rRNA due to the N-glycosidic activity of ricin toxin A chain, RTA. Since the extention of RTA by a mammalian-specific endoplasmic reticulum (ER) retention signal (KDEL) significantly increases RTA in vivo toxicity against mammalian cells, we here analyzed the phenotypic effect of RTA carrying the yeast-specific ER retention motif HDEL. Interestingly, such a toxin (RTAHDEL) showed a similar cytotoxic effect on yeast as a corresponding RTAKDEL variant on HeLa cells. Furthermore, we established a powerful yeast bioassay for RTA in vivo uptake and trafficking which is based on the measurement of dissolved oxygen in toxin-treated spheroplast cultures of S. cerevisiae. We show that yeast spheroplasts are highly sensitive against external applied RTA and further demonstrate that its toxicity is greatly enhanced by replacing the C-terminal KDEL motif by HDEL. Based on the RTA resistant phenotype seen in yeast knock-out mutants defective in early steps of endocytosis (∆end3) and/or in RTA depurination activity on 28S rRNA (∆rpl12B) we feel that the yeast-based bioassay described in this study is a powerful tool to dissect intracellular A/B toxin transport from the plasma membrane through the endosomal compartment to the ER. |
DOI der Erstveröffentlichung: | 10.3390/toxins3070834 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-278694 hdl:20.500.11880/29969 http://dx.doi.org/10.22028/D291-27869 |
ISSN: | 2072-6651 |
Datum des Eintrags: | 6-Nov-2020 |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Biowissenschaften |
Professur: | NT - Prof. Dr. Manfred Schmitt |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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toxins-03-00834.pdf | 707,79 kB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons