title: Cis and trans interactions between atlastin molecules during membrane fusion.
abstract: Atlastin (ATL), a membrane-anchored GTPase that mediates homotypic fusion of endoplasmic reticulum (ER) membranes, is required for formation of the tubular network of the peripheral ER. How exactly ATL mediates membrane fusion is only poorly understood. Here we show that fusion is preceded by the transient tethering of ATL-containing vesicles caused by the dimerization of ATL molecules in opposing membranes. Tethering requires GTP hydrolysis, not just GTP binding, because the two ATL molecules are pulled together most strongly in the transition state of GTP hydrolysis. Most tethering events are futile, so that multiple rounds of GTP hydrolysis are required for successful fusion. Supported lipid bilayer experiments show that ATL molecules sitting on the same (cis) membrane can also undergo nucleotide-dependent dimerization. These results suggest that GTP hydrolysis is required to dissociate cis dimers, generating a pool of ATL monomers that can dimerize with molecules on a different (trans) membrane. In addition, tethering and fusion require the cooperation of multiple ATL molecules in each membrane. We propose a comprehensive model for ATL-mediated fusion that takes into account futile tethering and competition between cis and trans interactions.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Tina Y
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Protein Sciences, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China;
authors.forename: Xin
authors.initials: X
authors.lastname: Bian
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Romano
authors.affiliation: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; and.
authors.forename: Tom
authors.initials: T
authors.lastname: Shemesh
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tom_rapoport@hms.harvard.edu.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Rapoport
authors.affiliation: Tianjin Key Laboratory of Protein Sciences, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Hu
mesh_terms: D000465:Algorithms; D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D059008:Time-Lapse Imaging; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; C543694:atl protein, Drosophila
keywords: GTPase; endoplasmic reticulum; lipid bilayer; membrane docking; spastic paraplegia type 3A gene
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