A possible docking and fusion particle for synaptic transmission

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Abstract
SEVERAL proteins have been implicated in the rapid (millisecond) calcium-controlled release of transmitters at nerve endings1,2, including soluble NV-ethylmaleimide-sensitive fusion protein (NSF3–5) and soluble NSF attachment protein (α-SNAP3,6), the synaptic SNAP receptor (SNARE)3,7 and the calcium-binding protein synaptotagmin2, which may function as a calcium sensor in exocytosis8. A second SNAP isoform (β-SNAP), which is 83% identical to α-SNAP, is highly expressed in brain9, 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 (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 β-SNAP from binding to synaptotagmin.