title: Physiological lipid composition is vital for homotypic ER membrane fusion mediated by the dynamin-related GTPase Sey1p.
abstract: Homotypic fusion of the endoplasmic reticulum (ER) is required for generating and maintaining the characteristic reticular ER membrane structures. This organelle membrane fusion process depends on the ER-bound dynamin-related GTPases, such as atlastins in animals and Sey1p in yeast. Here, to investigate whether specific lipid molecules facilitate GTPase-dependent ER membrane fusion directly, we comprehensively evaluated membrane docking and lipid mixing of reconstituted proteoliposomes bearing purified Sey1p and a set of ER-mimicking lipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and ergosterol. Remarkably, we revealed that each specific lipid species contributed little to membrane docking mediated by Sey1p. Nevertheless, Sey1p-dependent lipid mixing was strongly reduced by omitting three major acidic lipids from the ER-mimicking set and, moreover, was entirely abolished by omitting either phosphatidylethanolamine or ergosterol. Our reconstitution studies thus established that physiological lipid composition is vital for lipid bilayer rearrangements in GTPase-mediated homotypic ER membrane fusion.
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sugiura
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Mima
mesh_terms: D004721:Endoplasmic Reticulum / Q000502:physiology; D004875:Ergosterol / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008561:Membrane Fusion / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; C472231:SEY1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D004875:Ergosterol
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