title: Variable cooperativity in SNARE-mediated membrane fusion.
abstract: The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex drives the majority of intracellular and exocytic membrane fusion events. Whether and how SNAREs cooperate to mediate fusion has been a subject of intense study, with estimates ranging from a single SNARE complex to 15. Here we show that there is no universally conserved number of SNARE complexes involved as revealed by our observation that this varies greatly depending on membrane curvature. When docking rates of small (∼40 nm) and large (∼100 nm) liposomes reconstituted with different synaptobrevin (the SNARE present in synaptic vesicles) densities are taken into account, the lipid mixing efficiency was maximal with small liposomes with only one synaptobrevin, whereas 23-30 synaptobrevins were necessary for efficient lipid mixing in large liposomes. Our results can be rationalized in terms of strong and weak cooperative coupling of SNARE complex assembly where each mode implicates different intermediate states of fusion that have been recently identified by electron microscopy. We predict that even higher variability in cooperativity is present in different physiological scenarios of fusion, and we further hypothesize that plasticity of SNAREs to engage in different coupling modes is an important feature of the biologically ubiquitous SNARE-mediated fusion reactions.
authors.affiliation: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and.
authors.forename: Javier M
authors.initials: JM
authors.lastname: Hernandez
authors.affiliation: Center for Membrane Biology and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908.
authors.forename: Alex J B
authors.initials: AJ
authors.lastname: Kreutzberger
authors.affiliation: Center for Membrane Biology and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908.
authors.forename: Volker
authors.initials: V
authors.lastname: Kiessling
authors.affiliation: Center for Membrane Biology and Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908.
authors.forename: Lukas K
authors.initials: LK
authors.lastname: Tamm
authors.affiliation: Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany; and rjahn@gwdg.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
mesh_terms: D008081:Liposomes; D008561:Membrane Fusion / Q000502:physiology*; D050683:R-SNARE Proteins / Q000502:physiology; D050600:SNARE Proteins / Q000502:physiology*
chemical_list: D008081:Liposomes; D050683:R-SNARE Proteins; D050600:SNARE Proteins
keywords: exocytosis; fusion intermediate; liposome docking
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