Synaptic vesicle exocytosis.
Presynaptic nerve terminals release neurotransmitters by synaptic vesicle exocytosis. Membrane fusion mediating synaptic exocytosis and other intracellular membrane traffic is affected by a universal machinery that includes SNARE (for "soluble NSF-attachment protein receptor") and SM (for "Sec1/Munc18-like") proteins. During fusion, vesicular and target SNARE proteins assemble into an α-helical trans-SNARE complex that forces the two membranes tightly together, and SM proteins likely wrap around assembling trans-SNARE complexes to catalyze membrane fusion. After fusion, SNARE complexes are dissociated by the ATPase NSF (for "N-ethylmaleimide sensitive factor"). Fusion-competent conformations of SNARE proteins are maintained by chaperone complexes composed of CSPα, Hsc70, and SGT, and by nonenzymatically acting synuclein chaperones; dysfunction of these chaperones results in neurodegeneration. The synaptic membrane-fusion machinery is controlled by synaptotagmin, and additionally regulated by a presynaptic protein matrix (the "active zone") that includes Munc13 and RIM proteins as central components.
Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305, USA. tcs1@stanford.edu
Thomas C
TC
Südhof
Josep
J
Rizo
D000818:Animals; D005089:Exocytosis; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008561:Membrane Fusion; D051379:Mice; D008954:Models, Biological; D051938:Munc18 Proteins / Q000378:metabolism / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D017510:Protein Folding; D050600:SNARE Proteins / Q000378:metabolism / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology*; D050857:Synaptotagmins / Q000378:metabolism / Q000502:physiology
D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C107293:Rim protein, mammalian; D050600:SNARE Proteins; D050857:Synaptotagmins; D019204:GTP-Binding Proteins