title: Is lipid flippase activity of SNARE transmembrane domains required for membrane fusion?
abstract: It has been suggested that lipids translocate between the outer and inner leaflets of fusing membranes, or flip-flop, to facilitate changes in bilayer leaflet areas at various stages of fusion. Here, we investigated the lipid flip activity of synthetic peptides that mimic SNARE transmembrane domains (TMDs). These peptides indeed induce flip of marker lipids. However, mutations that reduce flip activity do not diminish fusogenicity and cholesterol blocks flip much more efficiently than fusion. Therefore, our data do not support a role for flip in membrane fusion. On the other hand, the ability of SNARE TMDs to catalyze flip is consistent with a role of SNAREs in biogenic lipid flip.
authors.affiliation: Lehrstuhl für Chemie der Biopolymere, Department für biowissenschaftliche Grundlagen, Technische Universität München, Freising, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Langer
authors.forename: Dieter
authors.initials: D
authors.lastname: Langosch
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D009154:Mutation; D057786:Peptidomimetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013569:Synapses / Q000378:metabolism; D050827:Syntaxin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008055:Lipids; D057786:Peptidomimetics; D050827:Syntaxin 1; D050988:Vesicle-Associated Membrane Protein 2; D002784:Cholesterol