title: Addition of lysophospholipids with large head groups to cells inhibits Shiga toxin binding.
abstract: Shiga toxin (Stx), an AB5 toxin, binds specifically to the neutral glycosphingolipid Gb3 at the cell surface before being transported into cells. We here demonstrate that addition of conical lysophospholipids (LPLs) with large head groups inhibit Stx binding to cells whereas LPLs with small head groups do not. Lysophosphatidylinositol (LPI 18:0), the most efficient LPL with the largest head group, was selected for in-depth investigations to study how the binding of Stx is regulated. We show that the inhibition of Stx binding by LPI is reversible and possibly regulated by cholesterol since addition of methyl-β-cyclodextrin (mβCD) reversed the ability of LPI to inhibit binding. LPI-induced inhibition of Stx binding is independent of signalling and membrane turnover as it occurs in fixed cells as well as after depletion of cellular ATP. Furthermore, data obtained with fluorescent membrane dyes suggest that LPI treatment has a direct effect on plasma membrane lipid packing with shift towards a liquid disordered phase in the outer leaflet, while lysophosphoethanolamine (LPE), which has a small head group, does not. In conclusion, our data show that cellular treatment with conical LPLs with large head groups changes intrinsic properties of the plasma membrane and modulates Stx binding to Gb3.
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Ieva
authors.initials: I
authors.lastname: Ailte
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Anne Berit Dyve
authors.initials: AB
authors.lastname: Lingelem
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Simona
authors.initials: S
authors.lastname: Kavaliauskiene
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.|Department of Research and Innovation, Østfold Hospital, Sarpsborg, Norway.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergan
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Audun Sverre
authors.initials: AS
authors.lastname: Kvalvaag
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Anne-Grethe
authors.initials: AG
authors.lastname: Myrann
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.
authors.forename: Tore
authors.initials: T
authors.lastname: Skotland
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.|Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D020383:Neutral Glycosphingolipids / Q000378:metabolism*; D011485:Protein Binding; D022621:Shiga Toxin / Q000494:pharmacology*; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D008246:Lysophospholipids; D020383:Neutral Glycosphingolipids; D047392:beta-Cyclodextrins; C091583:glycosphingolipid GalGb3; C108732:methyl-beta-cyclodextrin; D022621:Shiga Toxin