H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast

Björn Becker, Andrea Blum, Esther Gießelmann, Julia Dausend, Domenik Rammo, Nina C. Müller, Emilia Tschacksch, Miriam Steimer, Jenny Spindler, Ute Becherer, Jens Rettig, Frank Breinig, Manfred J. Schmitt*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)


A/B toxins such as cholera toxin, Pseudomonas exotoxin and killer toxin K28 contain a KDEL-like amino acid motif at one of their subunits which ensures retrograde toxin transport through the secretory pathway of a target cell. As key step in host cell invasion, each toxin binds to distinct plasma membrane receptors that are utilized for cell entry. Despite intensive efforts, some of these receptors are still unknown. Here we identify the yeast H/KDEL receptor Erd2p as membrane receptor of K28, a viral A/B toxin carrying an HDEL motif at its cell binding β-subunit. While initial toxin binding to the yeast cell wall is unaffected in cells lacking Erd2p, binding to spheroplasts and in vivo toxicity strongly depend on the presence of Erd2p. Consistently, Erd2p is not restricted to membranes of the early secretory pathway but extends to the plasma membrane where it binds and internalizes HDEL-cargo such as K28 toxin, GFPHDEL and Kar2p. Since human KDEL receptors are fully functional in yeast and restore toxin sensitivity in the absence of endogenous Erd2p, toxin uptake by H/KDEL receptors at the cell surface might likewise contribute to the intoxication efficiency of A/B toxins carrying a KDEL-motif at their cytotoxic A-subunit(s).

Original languageEnglish
Article number31105
JournalScientific Reports
Publication statusPublished - 5 Aug 2016
Externally publishedYes


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