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 1,2 , including soluble N V-ethylmaleimide-sensitive fusion protein (NSF 3–5 ) and soluble NSF attachment protein (α-SNAP 3,6 ), the synaptic SNAP receptor (SNARE) 3,7 and the calcium-binding protein synaptotagmin 2 , which may function as a calcium sensor in exocytosis 8 . A second SNAP isoform (β-SNAP), which is 83% identical to α-SNAP, is highly expressed in brain 9 , but its role is still unclear. Here we show that these proteins assemble cooperatively to form a docking and fusion complex. β-SNAP (but not α-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 (β-SNAP) to a calcium sensor (synaptotagmin). Polyphosphoinositols that block transmitter release, inositol 1,3,4,5-tetrakisphosphate (InsP 4 ), inositol 1,3,4,5,6-pentakisphosphate (InsP 5 ) and inositol 1,2,3,4,5,6-hexakisphosphate (InsP 6 ), also block the assembly of the particle by preventing β-SNAP from binding to synaptotagmin.