title: Lipid-anchored SNAREs lacking transmembrane regions fully support membrane fusion during neurotransmitter release.
abstract: Synaptic vesicle fusion during neurotransmitter release is mediated by assembly of SNARE- and SM-protein complexes composed of syntaxin-1, SNAP-25, synaptobrevin-2/VAMP2, and Munc18-1. Current models suggest that SNARE-complex assembly catalyzes membrane fusion by pulling the transmembrane regions (TMRs) of SNARE proteins together, thus allowing their TMRs to form a fusion pore. These models are consistent with the requirement for TMRs in viral fusion proteins. However, the role of the SNARE TMRs in synaptic vesicle fusion has not yet been tested physiologically. Here, we examined whether synaptic SNAREs require TMRs for catalysis of synaptic vesicle fusion, which was monitored electrophysiologically at millisecond time resolution. Surprisingly, we find that both lipid-anchored syntaxin-1 and lipid-anchored synaptobrevin-2 lacking TMRs efficiently promoted spontaneous and Ca(2+)-triggered membrane fusion. Our data suggest that SNARE proteins function during fusion primarily as force generators, consistent with the notion that forcing lipid membranes close together suffices to induce membrane fusion.
authors.affiliation: Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Taulant
authors.initials: T
authors.lastname: Bacaj
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yang
authors.forename: Zhiping P
authors.initials: ZP
authors.lastname: Pang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D050600:SNARE Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*; D050827:Syntaxin 1 / Q000235:genetics / Q000502:physiology; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000502:physiology
chemical_list: D008563:Membrane Lipids; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D050827:Syntaxin 1; D050988:Vesicle-Associated Membrane Protein 2