title: Membrane interaction of TNF is not sufficient to trigger increase in membrane conductance in mammalian cells.
abstract: Tumor necrosis factor TNF can trigger increases in membrane conductance of mammalian cells in a receptor-independent manner via its lectin-like domain. A lectin-deficient TNF mutant, lacking this activity, was able to bind to artificial liposomes in a pH-dependent manner, but not to insert into the bilayer, just like wild type TNF. A peptide mimicking the lectin-like domain, which can still trigger increases in membrane currents in cells, failed to interact with liposomes. Thus, the capacity of TNF to trigger increases in membrane conductance in mammalian cells does not correlate with its ability to interact with membranes, suggesting that the cytokine does not form channels itself, but rather interacts with endogenous ion channels or with plasma membrane proteins that are coupled to ion channels.
authors.affiliation: Department of Biochemistry, Sciences II, University of Geneva, Switzerland. gisou.vandergoot@biochem.unige.ch
authors.forename: F G
authors.initials: FG
authors.lastname: van der Goot
authors.forename: J
authors.initials: J
authors.lastname: Pugin
authors.forename: M
authors.initials: M
authors.lastname: Hribar
authors.forename: L
authors.initials: L
authors.lastname: Fransen
authors.forename: Y
authors.initials: Y
authors.lastname: Dunant
authors.forename: P
authors.initials: P
authors.lastname: De Baetselier
authors.forename: A
authors.initials: A
authors.lastname: Bloc
authors.forename: R
authors.initials: R
authors.lastname: Lucas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D002942:Circular Dichroism; D004926:Escherichia coli; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000235:genetics
chemical_list: D002712:Chlorides; D007473:Ion Channels; D008081:Liposomes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha