A possible docking and fusion particle for synaptic transmission.
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.
Schiavo
G
G
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Gmachl
M J
MJ
Stenbeck
G
G
Söllner
T H
TH
Rothman
J E
JE
D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D009435:Synaptic Transmission / Q000502:physiology*; D050857:Synaptotagmins; D033921:Vesicular Transport Proteins
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D007295:Inositol Phosphates; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins; D005982:Glutathione Transferase; D052066:N-Ethylmaleimide-Sensitive Proteins; D002118:Calcium