Turbocharging Synaptic Transmission.

Evidence from biochemistry, genetics, and electron microscopy strongly supports the idea that a ring of Synaptotagmin contributes importantly to clamping and release of synaptic vesicles for synchronous neurotransmission. Recent direct measurements in cell-free systems suggest there are 12 SNAREpins in each ready-release vesicle, consisting of 6 peripheral and 6 central SNAREpins. The 6 central SNAREpins are directly bound to the Synaptotagmin ring, are directly released by Ca++ , and they initially open the fusion pore. The 6 peripheral SNAREpins are indirectly bound to the ring, each linked to a central SNAREpin by a bridging molecule of Complexin. We suggest that the primary role of peripheral SNAREpins is to provide additional force to "turbocharge" neurotransmitter release, explaining how it can occur much faster than other forms of membrane fusion. The synaptic vesicle protein Synaptophysin forms hexamers which bear 2 copies of the v-SNARE VAMP at each vertex, one likely assembling into a peripheral SNAREpin and the other into a central SNAREpin.