A possible docking and fusion particle for synaptic transmission

• Published in: Nature (London) Vol. 378; no. 6558; pp. 733 - 736
• Main Authors: Schiavo, Giampietro, Gmachl, Michael J. S, Stenbeck, Gudrun, Söllner, Thomas H, Rothman, James E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 14.12.1995; Nature Publishing Group
• Subjects: Biochemistry; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium-Binding Proteins; Carrier Proteins - metabolism; Carrier Proteins - physiology; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Glutathione Transferase - metabolism; Inositol Phosphates - metabolism; Membrane Glycoproteins - metabolism; Membrane Glycoproteins - physiology; Membrane Proteins - metabolism; Membrane Proteins - physiology; N-Ethylmaleimide-Sensitive Proteins; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - physiology; Protein Binding; Proteins; Recombinant Fusion Proteins - metabolism; SNARE Proteins; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; Synaptic Transmission - physiology; Synaptotagmins; Vertebrates: nervous system and sense organs; Vesicular Transport Proteins; Vertebrata; Membrane protein; Synapse; Mammalia; Synaptic transmission; Central nervous system; Ox; Artiodactyla; Fusion protein; Ungulata; Brain (vertebrata)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/378733a0

Several proteins have been implicated in the rapid (millisecond) calcium-controlled release of transmitters at nerve endings, including soluble N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (alpha-SNAP), the synaptic SNAP receptor (SNARE) and the calcium-binding protein synaptotagmin, which may function as a calcium sensor in exocytosis. A second SNAP isoform (beta-SNAP), which is 83% identical to alpha-SNAP, is highly expressed in brain, but its role is still unclear. Here we show that these proteins assemble cooperatively to form a docking and fusion complex. beta-SNAP (but not alpha-SNAP) binds synaptotagmin and recruits NSF, indicating that the complex may link the process of membrane fusion to calcium entry by attaching a specialized fusion protein (beta-SNAP) to a calcium sensor (synaptotagmin). Polyphosphoinositols that block transmitter release, inositol 1,3,4,5-tetrakisphosphate (InsP4), inositol 1,3,4,5,6-pentakisphosphate (InsP5) and inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), also block the assembly of the particle by preventing beta-SNAP from binding to synaptotagmin.