title: H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast.
abstract: 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, GFP(HDEL) 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).
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Björn
authors: B
authors: Becker
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Andrea
authors: A
authors: Blum
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Esther
authors: E
authors: Gießelmann
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Julia
authors: J
authors: Dausend
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Domenik
authors: D
authors: Rammo
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Nina C
authors: NC
authors: Müller
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Emilia
authors: E
authors: Tschacksch
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Miriam
authors: M
authors: Steimer
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Jenny
authors: J
authors: Spindler
authors: Institute of Physiology, Saarland University, D-66421 Homburg, Germany.
authors: Ute
authors: U
authors: Becherer
authors: Institute of Physiology, Saarland University, D-66421 Homburg, Germany.
authors: Jens
authors: J
authors: Rettig
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Frank
authors: F
authors: Breinig
authors: Molecular and Cell Biology, Department of Biosciences (FR 8.3) and Center of Human and Molecular Biology (ZHMB), Saarland University, D-66123 Saarbrücken, Germany.
authors: Manfred J
authors: MJ
authors: Schmitt
mesh_terms: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D055646:Killer Factors, Yeast / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013104:Spheroplasts
chemical_list: C064922:ERD2 protein, S cerevisiae; D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; C060153:KAR2 protein, yeast; C064459:KDEL receptor; D055646:Killer Factors, Yeast; D008565:Membrane Proteins; D018000:Receptors, Peptide; D029701:Saccharomyces cerevisiae Proteins